Registration Dossier

Administrative data

Description of key information

  1,2-Diaminotoluene, propoxylated (CAS 1228577-90-9) (analogue substance 2) was evaluated in a 28 day oral gavage repeat-dose protocol (OECD 407) in rats.  Dosing levels tested were 0, 40, 160 and 640 mg/kg/d.  Decreases in food consumption and body weights were observed in the high dose group and liver hypertrophy accompanied by changes in clinical chemistry were reported at the mid and high-dose groups.  There were no signs of neurological effects and no other findings considered relevant to human health.  The NOAEL from the study was 40 mg/kg/day based on the hepatic effects. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
40 mg/kg bw/day

Additional information

Read across justification

A repeat dose toxicity (oral) study is not available on the substance Oligomeric reaction product of formaldehyde, aniline and 2-methyloxirane, and reaction product of 2,2'-oxydiethanol and 2-methyloxirane (EC917-215-9) (target substance), therefore data has been used from 1,2-Diaminotoluene, propoxylated (CAS 1228577-90-9) (analogue substance 2) to address this data gap.

See section 13 for the read-across justification report.

 

Target substance:

Based on available toxicological data, the target substance has a low order of toxicity (LD50 > 2000 mg/kg), is not irritating to eye or skin and has a low potential for genotoxicity. The target substance is a dermal sensitiser.

 

Analogue 2 substance:

Analogue substance 2 (CAS 1228577-90-9) has a low order of toxicity (LD50 > 2000 mg/kg), is not irritating to eye or skin, is not a dermal sensitiser, has a low potential for genotoxicity and is not toxic to reproduction or development.

 

Repeated dose toxicology data:

Analogue substance 2 was evaluated in a 28 day oral gavage repeat-dose protocol (OECD 407) in rats. Dosing levels tested were 0, 40, 160 and 640 mg/kg/d. Decreases in food consumption and body weights were observed in the high dose group and liver hypertrophy accompanied by changes in clinical chemistry were reported at the mid and high-dose groups. There were no signs of neurological effects and no other findings considered relevant to human health. The NOAEL from the study was 40 mg/kg/day based on the hepatic effects.  

 

There is a slight bias anticipated in using the analogue 2 substance as a read-across to predicting effects of the target substance. Analogue 2 is likely to be more bioavailable after oral administration than the target substance. This increase in potential bioavailability for the analogue substance would make it worse-case with respect to the target substance. Thus, the results from the analogue substance have the potential to over-predict the effects of the target substance when based on administered dose. 

 

Conclusion

The available data demonstrates a pattern of similar and limited toxicological properties across the target and analogue substances. It is postulated that any differences observed may be accounted for by the increased surfactant activity of the target substance. 

Therefore, it is concluded that read across is appropriate and repeated dose toxicological data can be used from analogue 2 to the target substance.

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, chapter 3.9 classification of Diaminotoluene, propoxylated as STOT RE cat. 2 is not recommended.

Although the LOAEL (160 mg/kg) is below the guidance value for 28-day studies (300 mg/kg), the nature and severity of the adverse effects at this dose level do not support classification.

Hematological changes at 160 mg/kg (females) and even at 640 mg/kg (females/males) give no conclusive evidence of consistent and significant adverse effect in hematology.

The periportal hepatocellular changes observed at 160 mg/kg (2/5 males and 5/5 females grade 2) and even at 640 mg/kg (5/5 male and 5/5 female, grade 3) give no evidence of multifocal or diffuse necrosis, fibrosis or granuloma formation. The morphological alterations comply with those typical for reversible hepatic changes due to liver enzymes induction reflecting increased metabolism and hepatic clearance of Diaminotoluene, propoxylated. The follicular cell hyperthrophy/hyperplasie in the thyroids, observed in both genders up to a moderate degree at 160 mg/kg (grade 2) and 640 mg/kg (grade 3), are interpreted as being a specific thyroid toxicity via liver enzyme induction.