Dermal subchronic toxicity studies

In the risk assessment, some steps are not well described. For example, subchronic toxicity studies and not chronic toxicity studies are used in the risk assessment. Exposure duration and frequency considerations are not discussed. Route-to-route extrapolation is considered acceptable implicitly, without further evaluation of the various issues involved. The rationale for using a dermal absorption default of 10 %, in the absence of data is also not discussed. 

Toxicity studies on trifluoroethanol show acute oral LD q, 240 mg/kg acute dermal LD q, 1680 mg/kg and acute inhalation L(ct) Q, 4600 ppmh. Long-term subchronic inhalation exposure to 50—150 ppm of the alcohol has caused testicular depression in male rats, but no effects were noted at the 10 ppm level (32). Although the significance of the latter observations for human safety is unknown, it is recommended that continuous exposure to greater than 5 ppm or skin contact with it be avoided. 

Much toxicological data are available on this red pigment acute oral toxicity in mice, 90-day subchronic toxicological study, acute dermal irritation and corrosion, acute eye irritation and corrosion, anti-tumor effectiveness, micronucleus test in mice, AMES test Salmonella typhimurium reverse mutation assay), estimation of antibiotic activity, and results of estimation of five mycotoxins. A new patent on Arpink Red was filed in 2001 with claims of anti-cancer effects of the anthraquinone derivatives and apphcations in the food and pharmaceutical fields. 

AALAC certified laboratory. In-housing testing included acute, subacute, and subchronic oral, dermal and inhalation studies and specialty reproductive, behavioural, haematological and renal function toxicity studies. Preparation of risk assessment, submissions and presentations to regulatory agencies and trade association. 

In the test guidelines for 90-day dermal (OECD TG 411) and inhalation (OECD TG 413) toxicity studies, the following definition in relation to the term subchronic is provided Subchronic dermal/inhalation toxicity is the adverse effects, which follow repeated daily dermal application/ inhalation of a chemical for part (not exceeding 10%) of a life span. ... 

Abdel-Rahman MS, Skowronski GA, Turkall RM, et al. 1987b. Subchronic dermal toxicity studies of Alcide Allay gel and liquid in rabbits. J Appl Toxicol 7(5) 327-333. 

DePass, L.R., Fowler, E.H. Letmg, H.-W. (1995) Subchronic dermal toxicity study of triethanolamine in C3H/HeJ mice. Food chem. Toxicol., 33, 675-680 Dean, B.J., Brooks, T.M., Hodson-Walker, G Hutsorr, D.H. (1985) Genetic toxicology testing of 41 industrial chemicals. Mutat. Res., 153, 55-77... 

Acute dermal toxicity is the study of adverse effects occurring within a short time of dermal application of a single-dose test chemical. In evaluating the safety of a chemical, determination of acute dermal toxicity is useful when exposure by the dermal route is likely and more predominant. It provides information on health hazards likely to arise from short-term exposure by the dermal route. Data from an acute dermal toxicity study may serve as a basis for chemical classification and labeling. It is an initial step in establishing a dose regimen in subchronic (and other) studies, and may provide information on dermal absorption as well as a chemical s mode of toxic action. 

At least three dose levels with a control and (where appropriate) a vehicle control should be used in a subchronic dermal toxicity study. Expect for treatment with the test chemical, the control group should be handled in a manner identical to the test group. The highest-dose level of the test chemical should result in toxic effects but not produce fatalities, which would prevent a meaningful evaluation of the results. The lowest-dose level of the test chemical should not produce evidence of toxicity. Where there is a usable estimation of human exposure, the lowest level should exceed this. Ideally, the intermediate-dose level(s) of the chemicals should produce minimal observable toxic effects. If more than one intermediate dose is used, the dose levels should be spaced to produce gradation of toxic effects. In the low and intermediate groups and in the controls, the incidence of fatalities should be low to permit a meaningful evaluation of results. 

The database for the health effects of 1,1-dichloroethane in experimental animals is lacking, and the studies reviewed consisted primarily of one subchronic inhalation study, one inhalation developmental toxicity study, and two oral chronic bioassays. No information is available on the effects of 1,1-dichloroethane following dermal exposure. The limited information available in animals suggests that 1,1-dichloroethane may be nephrotoxic, fetotoxic, and possibly carcinogenic. The data also indicate that 1,1-dichloroethane is considerably less toxic than 1,2-dichloroethane and the tetrachlorinated aliphatics. 

A 90 day subchronic oral study in rat and 21 day dermal study in rabbit provided no-observed-ad-verse-effect levels (NOAELs) of 3.3 and 100 mg kg day , respectively. Prenatal developmental toxicity study in female Sprague-Dawley rats exposed to atrazine during gestation day 6 through day 15 demonstrated maternal and developmental NOAELs of 25 mg kg day ... 

The subchronic toxicity of EGBE has been examined in animals via oral, inhalation, and dermal routes of exposure. The lowest no-observed-effect level (NOEL) in an oral subchronic study was 80 mg kg for rats administered EGBE in feed over a 90 day period. Inhalation exposure of rats for 13 weeks, 6h day , 5 days week to EGBE vapors at 25-77 ppm indicated an NOEL of 25 ppm. In a 90 day dermal study of rabbits, EGBE was applied 6 h day, 5 days week at doses up to 150 mg kg There was no evidence of systemic toxicity or skin irritation at the site of application at any of the dose levels tested. 

CMA. 1983. 90-Day subchronic dermal toxicity study in rabbits with ethylene glycol monobutyl ether with cover sheet dated 06/12/89. EPA/OTS Doc 86-890000726. 

Subchronic Oral Dosing Studies Subchronic 21-Day Dermal Toxicity Study Subchronic 90-Day Dermal Toxicity Study Subchronic Inhalation Toxicity Study Subchronic Neurotoxicity Studies... 

Of concern to the group was the proposal to require 90-day subchronic dermal toxicity studies in animals. Current requirements specify a 21-day rabbit dermal study which takes 6 months at a cost of about U0,000. The proposed 90-day study would cost about 100,000 and would provide no additional useful information. The question remains as to whether the study should be done with only the parent compound or with each formulated product due to potential effect of surfactants and solvents on the rate of absorption of the active ingredient(s) into the exposed subjects. 

Hoechst. 1985c. Endosulfan - active ingredient technical (code HOE 02671 OIZD97 0003) Testing for subchronic dermal toxicity - 21 applications over 30 days - in Wistar rats. Hoechst Aktiengesellschaft, Frankfurt, Germany. Report no. 84.0223. [unpublished study]... 

Subchronic Dermal Toxicity 90-Day Study (Original Guideline, adopted 12 May 1981)... 

Neurotoxicity. No histopathological effects on organs and tissues of the neurological systems of animals were found in subchronic and chronic oral studies, but signs of central nervous system toxicity were reported in inhalation, oral, and dermal studies. A battery of tests for neurotoxicity would provide further information of the neurotoxicity in animals, which then might be related to possible neurotoxic effects in humans. 

Subchronic studies49 in rabbits treated dermally with 35 resulted in testicular atrophy and spermatogenic depression. The material is also active, when applied by the oral route. Toxicity and reproductive studies in male rats and monkeys showed that 35 is likewise active p.o. in rats and monkeys but inactive in monkeys when administered dermally at daily doses over an extended period of time. Further studies50 showed that 35 interrupts the normal oestrous cycle in mature female rats. 

Subchronic dermal toxicity is the study of adverse effects occurring as a result of the repeated daily dermal application of a test chemical to animals for a part (not exceeding 10%) of the life span. In the evaluation of a chemical s toxic characteristics, the determination of subchronic dermal toxicity may be performed after initial information on toxicity has been obtained by acute testing. This study provides information on health hazards likely to arise from repeated exposure via the dermal route over a limited period of time. 

---