Formaldehyde, oligomeric reaction products with aniline

Carcinogenicity

Description of key information

in summary, MDA was carcinogenic in rats and mice after oral long-term administration.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

LOAEL

9 mg/kg bw/day

Justification for classification or non-classification

In regulation 1272/2008/EC, MDA is officially classified as carcinogen 1B, H350: may cause cancer.

According directive 67/548/EC, MDA is classified as carcinogen category 2: R45: may cause cancer.

Additional information

Justification on read-across of data for the 4,4´-isomer of MDA for oligomeric MDA in the scope of REACH is documented in IUCLID Toxicological information and described in sections 5.1 and 5.11 of the CSR.

Discussion

The most relevant assessment of carcinogenicity in animals comes from a 2-year study with 4,4'-methylenedianiline dihydrochloride

(MDA) in F344 rats and B6C3F1 mice (NTP, 1983; Weisburger et al., 1984; Lamb et al., 1986).In this study both species were administered via the drinking water with 0, 150 and 300 ppm MDA over a period of 103 weeks. The calculated average intake of MDA in low and high dose was 9 and 16 mg/kg bw/day for male rats, 10 and 19 mg/kg bw/day for female rats, 25 and 58 mg/kg bw/day for male mice as well as 19 and 43 mg/kg bw/day for female mice. Under the conditions of this study MDA was clearly carcinogenic for both species producing thyroid and liver tumors.

In rats, significantly increased incidences of thyroid follicular cell carcinomas in males, thyroid follicular cell adenomas in females, C-cell adenomas of the thyroid gland in females as well as neoplastic nodules in the liver of males were observed. Cystic and hyperplastic follicular thyroid lesions were increased in high dose females. Rats of each dose group showed toxic liver effects (fatty metamorphosis, focal cellular change). An increased incidence of renal mineralization was evident in high dose males. Survival was comparable among all groups. High dose female rats had lower mean body weights than those of the controls. No compound-related clinical signs were observed.

In mice, significantly increased incidences of thyroid follicular cell adenomas and hepatocellular carcinomas in males and females, adenomas of the liver and malignant lymphomas in females as well as adrenal pheochromocytomas in males were seen. Hyperplastic follicular thyroid lesions were increased in high dose mice of both sexes. Liver cell degeneration was observed with high incidences in males at 150 and 300 ppm and to a lesser extent in high dose females. An increased incidence of kidney nephropathy was evident in all dose groups and renal papillary mineralization was greater in males and females at 300 ppm compared to controls. Survival was reduced in high dose males. High dose groups showed reduced mean body weights from week 16 onwards. No compound-related clinical signs were observed.

Carcinogenicity: via oral route (target organ): digestive: liver; glandular: thyroids