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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

90-Day rat feeding study; OECD 408; LOAEL (males): 4200 ppm (equivalent to 279 mg/kg bw/day); LOAEL (females): 14000 ppm (equivalent to 1140 mg/kg bw/day). Reliability = 1

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
279 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
GLP, guideline study
System:
endocrine system
Organ:
pituitary gland
thyroid gland

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Groups of 10 male and 10 female rats received daily oral dietary concentrations of 0, 120, 700, 4200, or 14000 ppm of the test item for 90 or 91 consecutive days. Test item-related effects were noted in body weight and food intake parameters in males (adverse) and females (non-adverse) at 14000 ppm. Test item related potentially adverse histopathological findings included thyroid follicular cell hypertrophy (>4200 ppm in males and at 14000 ppm in females), individual cell hypertrophy of the pars distalis of the pituitary (>4200 ppm, males only), and hepatocellular vacuolation (14000 ppm in males and females). The NOAEL for male rats was 700 ppm, which is equivalent to 47 mg/kg bw/day. This NOAEL is based on thyroid follicular cell hypertrophy and pituitary pars distalis individual cell hypertrophy at 4200 ppm (279 mg/kg bw/day) and above. The NOAEL for the female rats was 4200 ppm, which is equivalent to 313 mg/kg bw/day. This NOAEL was based on hepatocellular vacuolation, and thyroid follicular cell hypertrophy at 14000 ppm (1140 mg/kg bw/day). The LOAEL for male and female rats were 4200 and 14000 ppm (equivalent to 279 and 1140 mg/kg bw/day), respectively. The thyroid follicular cell hypertrophy is potentially adverse in rats, but not relevant to humans.
Rats were fed a diet containing 0, 120, 715, 4280, or 12050 ppm test substance for approximately 9 weeks in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test. The systemic toxicity NOAEL was 4280 ppm, based on potentially adverse effects observed at 12050 ppm consisting of microscopic effects on the thyroid gland and body weight effects in P1 males and effects on body weight and food consumption parameters in P1 females during gestation and lactation. While the effects on the thyroid gland are potentially adverse to the rat, they are of questionable relevance to humans.

Justification for classification or non-classification

Based on the LOAEL of 279 mg/kg bw/day in a repeated dose dietary study, the substance does not need to be classified for repeated dose toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.