Registration Dossier

Administrative data

Description of key information

28-day oral (gavage)  NOAEL for both sexes was concluded as 40 mg/kg b.w./d ( based on nominal) based on histopathological changes in the liver and thyroids (read across from oTDA, propoxylated).

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

Results 'read across' from study on oTDA, propxylated, as permitted by Annex XI para 1.5, based on the justification in the report by Paul Illing Consultancy Services Ltd. and Marlin Consultancy (Illing and Barratt, 2010). Thus, on animal welfare grounds this test should not be undertaken on oTDA, ethoxylated and propoxylated. For further details concerning the grouping, consult Illing and Barratt, 2010. 

The NOAEL for both sexes was concluded as 40 mg/kg b.w. /d (based on nominal).  



Repeated dose toxicity: inhalation - systemic effects (target organ) digestive: liver; glandular: thyroids

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.The species-specific mechanism/effect of toxicity observed in this study cannot be directly extrapolated to humans, i.e. these effects are therefore considered of insufficient concern for classification.

 

On the basis of 'read across' from oTDA, propoxylated, the findings in the available study do not warrant classification ofDiaminotoluene, ethoxylated and propoxylated according to the EU criteria.