Carcinogens, mutagens, or reproductive

The deadlines for registration are set according to the volume of the substance on the market or the hazard. The shortest deadlines apply to very high volume substances (above 1000 tonnes), and carcinogenic, mutagenic or reproduction toxic substances above 1 tonne. These will have to be registered within 3 years. 

Substances that are carcinogenic, mutagenic, or reproductively toxic (i.e., CMRs), for example, some endocrine disrupters, may pose special problems for derivation of aquatic EQSs (e.g., lack of internationally agreed tests in some cases difficulties with prediction of safe concentrations), but use of special tests for these properties is only justified for a small subset of chemicals that meet clear criteria. Furthermore, EQSs for these substances should not be derived directly from in vitro data or from biomarkers of exposure but from in vivo tests alone. 

I.e. prioritization criteria according to REACH Annex III Indications that the substance is classifiable as a carcinogen, mutagen or reproductive toxicant in categories lor 2, substances with at least one classifications according to 67/548, substances that are PBT or vPvB (according to the REACH criteria). 

Avoid the discharge of carcinogenic, mutagenic or reproduction toxic chemicals, as well as chemicals whose metabolites exhibit these properties. 

Table 3.20 Classification for carcinogenic, mutagenic, or reproductive properties.

Substances produced or imported in quantities of up to 1 tonne for which it is predicted that they are likely to meet the criteria for category 1 or 2 classification for carcinogenicity, mutagenicity, or reproductive toxicity, the following properties have to be investigated and submitted to the Agency ... 

Known or suspected carcinogens, mutagens, or reproductive toxicants (CMRs)... 

Aerosolized pentamidine is FDA approved for the treatment and prophylaxis of some types of pneumonia. Pentamidine administered as an aerosol must be reconstituted from a lyophilized powder. No studies exist to evaluate the potential carcinogenic, mutagenic, or reproductive effects of pentamidine. Studies among healthcare workers reveal uptake by those personnel who administer the drug. Side effects include coughing, sneezing, mucous membrane irritation, headache, and bronchospasms. 

In Europe, after publication of several extensive analyses and risk assessments for a number phthalate esters, several phthalates with the C4-C6 backbones were listed with a Category 2 or Category 3 CMR (Carcinogenic, Mutagenic, or Reproductively-toxic)... 

Meanwhile the first tranche of the registration is done for all chemicals with a market volume of more than 1,000 Mg/a and for chemicals which have a high concern out of hazardous reasons (e.g., carcinogenic, mutagenic, or toxic to reproduction (CMR)). By the REACH deadline of 30 November 2010 for the first tranche, 24,675 registration dossiers were submitted for 4,300 substances including nearly... 

Manufactured or imported in quantities >1 t/a and meeting the criteria for classification as carcinogenic, mutagenic, or toxic to reproduction category 1 or 2 (DSD) and category lA or IB (CLP), respectively... 

Timing for carcinogenic, mutagenic, or toxic for reproduction substances (CMR), very toxic, and R50/53 substances is as follows ... 

NOEC or NOEL from long-term avian and mammalian feeding studies Mammalian toxicity data (oral toxicity, repeated dose toxicity, carcinogenicity, mutagenicity, and reproduction studies) QSAR outputs... 

Aspartame is not toxic, carcinogenic, mutagenic, or teratogenic, and has no effect on reproduction. 

The cosmetics industry is another chemical chooser ripe for change. The European Union amended its Cosmetics Directive in January 2003 to outlaw carcinogens, mutagens, and reproductive toxicants in cosmetics. Member states of the European Union are required to comply by September 2004.71 Not only will companies marketing cosmetics in Europe need to change formulations, but companies marketing cosmetics in the United States will either need to follow suit or argue to American women that they need not worry about the risks from such chemicals. These and other such choices will flow down the supply chain to chemical producers. 

The hepatotoxicity (Fell etal. 1996), pulmonary toxicity and reproductive and developmental toxicity of manganese may also be relevant in humans (Frumkin and Solomon 1997), whilst carcinogenic, mutagenic or teratogenic effects in mammals have not been confirmed (Saric 1986 Schiele 1991). 

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