3-methoxy-3-methylbutan-1-ol

Carcinogenicity

Description of key information

no study available, however, based on the results of available repeated dose toxicity studies it has been concluded that there is no indication of carcinogenicity

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

A carcinogenicity study is listed in Column 1 (standard information required) of Annex X (8.9.1) of the REACH Regulation, but is not usually required. Column 2 (specific rules for adaptation from Column 1) of Annex X states that a carcinogenicity study may be proposed (by the registrant) or requested (by ECHA) if:

(1) the substance has a widespread dispersive use or there is evidence of frequent or long-term human exposure, and;

(2) the substance is classified as germ cell mutagen category 2 or there is evidence from the repeated dose study(ies) that the substance is able to induce hyperplasia and/or pre-neoplastic lesions.

For the registered substance, the supported uses include widespread dispersive use, with the potential for frequent or long-term human exposure. However, in order for a carcinogenicity study to be proposed (or required), the hazard profile of the substance also needs to be considered.
Specifically, there is no evidence of genotoxic effects in studies in vitro (OECD 471, OECD 476, OECD 473), demonstrating that the substance does not cause gene mutations or chromosomal aberrations. Consequently, testing in vivo is not required, and the substance is not classified (or proposed to be classified) as Mutagen Category 2.

The key study for repeated dose toxicity is the 90-day oral toxicity (OECD 408). This study used dose levels of up to 1000 mg/kg bw/d, and included histopathological assessment of the adrenals, gross lesions, aorta, brain (including medulla/pons, cerebellar and cerebral cortex), caecum, colon, duodenum, epididymides, eyes with optic nerve and Harderian gland, femur with knee joint, heart, ileum (including Peyer´s patches), jejunum , kidneys, liver, lungs, lymph nodes (mandibular, mesenteric, axillary), mammary gland (male and female), oesophagus, ovaries, oviducts, pancreas, pituitary, prostate and seminal vesicles with coagulating glands, rectum, salivary glands (sublingual, submandibular), sciatic nerve, skeletal muscle, skin , spinal cord (cervical, thoracic and lumbar segments), spleen, sternum (with bone marrow), stomach, testes, thymus, thyroid gland including parathyroid glands, tongue, trachea, ureters, urinary bladder, uterus with cervix and vagina. The study did not identify any treatment-related hyperplastic or pre-neoplastic lesions. Microscopic treatment-related findings were limited to the liver of females at 250 and 1000 mg/kg bw/d. These rats showed an increase of inflammatory cell foci in the liver. In the absence of necrosis, Kupffer cell proliferation, apoptosis, fibrosis, alteration in liver function and no significant increase in serum ALT or AST activities, this finding was considered to be of a non-adverse.

ECHA REACH Guidance (Chapter R.7a; R.7.7.13.2) states that ‘For substances for which there is no concern for mutagenic activity, and no other toxicological indicators of concern for carcinogenicity (i.e. for the substance itself or for structurally-related substances), there is no need for further consideration of its carcinogenic potential. This applies equally to those substances at the Annex X tonnage level as to those at lower tonnage levels.’ The Guidance further states that ‘for non-genotoxic substances, toxicological indicators of concern are available (e.g. hyperplastic or pre-neoplastic lesions in repeated dose toxicity studies of the substance itself and/or of closely related substances), they should be investigated further on a case-by-case basis. Any decision on further testing is dependent upon the type and strength of the indications for carcinogenicity, the potential mechanism of action and their relevance to humans, and the type and level of human exposure.’

For the registered substance, in the absence of any evidence of genotoxic activity and in the absence of any evidence of hyperplastic or pre-neoplastic lesions in repeated dose toxicity studies, it can be concluded that there is no indication of carcinogenicity. Consequently, a carcinogenicity study is not scientifically justified and is not proposed for the substance. This is consistent with Column 2 of Annex X and Article 25 of the REACH Regulation, which states that animal testing shall be undertaken only as a last resort.

Justification for classification or non-classification

Carcinogenicity studies have not been conducted for MMB.

However, in the absence of any evidence of genotoxic activity and in the absence of any evidence of hyperplastic or pre-neoplastic lesions in repeated dose toxicity studies, it can be concluded that there is no indication of carcinogenicity. Consequently, a carcinogenicity study is not scientifically justified and is not proposed for the substance. This is consistent with Column 2 of Annex X and Article 25 of the REACH Regulation, which states that animal testing shall be undertaken only as a last resort.