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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Key value for chemical safety assessment

Effects on fertility

Description of key information

Data waiving: A screening study for reproductive / developmental toxicity does not need to be conducted because a pre-natal developmental toxicity study is available.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

Oral: NOAEL (systemic, rat, female) = 200 mg/kg bw/day for maternal animals (based on read-across)

Oral: NOAEL (developmental, rat, male/female) = 600 mg/kg bw/day for offspring (based on read-across)

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
food consumption and compound intake
mortality
other: observation of one spontaneous death in the high dose group with no identified cause of death.
Key result
Abnormalities:
no effects observed
Key result
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
>= 600 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse or treatment-related effects were observed up to and including the highest tested dose level.
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Based on the results in this prenatal developmental toxicity study the maternal No Observed Adverse Effect Level (NOAEL) for Reaction mass of 2,2'-[(4-methylphenyl)imino]bisethanol and Ethanol 2-[[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino]- (EC911-490-9) was established at 200 mg/kg bw/day. The offspring and developmental NOAEL was established at 600 mg/kg bw/day, the highest dose tested. Applying the read-across approach, similar results are expected for the target substance N,N-Dihydroxyethyl-p-toluidine (CAS 3077-12-1).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
600 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no data available regarding toxicity to reproduction for N,N-Dihydroxyethyl-p-toluidine (CAS 3077-12-1). Therefore, read-across from an appropriate structural analogue substance is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.7. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13). Information from the analogue substance Reaction mass of 2,2'-[(4-methylphenyl)imino]bisethanol and 2-[[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino]-ethanol (EC 911-490-9) will be taken into account to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.7.

Reaction mass of 2,2'-[(4-methylphenyl)imino]bisethanol and 2-[[2-(2-hydroxyethoxy)ethyl](4-methylphenyl)amino]-ethanol (EC 911-490-9) was tested in a pre-natal developmental toxicity study according to OECD 414 and in compliance with GLP. Mated female Wistar Han rats were assigned to four dose groups, each containing twenty-two animals (Charles River, 2017b). The test substance was administered once daily by gavage from Day 6 to 20 post-coitum at doses of 60, 200 and 600 mg/kg bw/day. The rats of the control group received the vehicle, propylene glycol, alone. Accuracy and homogeneity of formulations were demonstrated by analyses. Regarding maternal findings, one female of the 600 mg/kg bw/day group was found dead on Day 20 post-coitum. This female showed tonic spasms directly after dosing but recovered after two minutes. Body weight and food consumption were considered to be normal for this female and at necropsy, no macroscopic findings were noted. This female was pregnant and had 13 fetuses, of which no external abnormalities were noted. The reason for this spontaneous death could not be identified, but a relationship to treatment cannot be excluded.

Remarkable clinical signs of toxicity (i.e. rales, piloerection, smacking, lethargy, salivation and hypothermia) in addition to significant body weight loss and reduced food consumption were noted for one single female treated at 600 mg/kg bw/day which did not die during the study. Moreover, the gastrointestinal tract was distended with gas, adrenal glands were enlarged and the spleen and thymus were reduced in size. These findings correlated with the observations during the in-life phase of this female. A treatment relation of these observations in a single female is unlikely but cannot be excluded. Some of the remaining females treated at 600 mg/kg bw/day also showed treatment-related and toxicologically relevant effects. Rales was noted for four females, and tremor and lethargy were noted both for three females at 600 mg/kg bw/day. Statistically significantly lower mean body weight gain (incl. corrected for gravid uterus) and food consumption were noted from Day 9 post-coitum onwards and from Day 6 to Day 15 post-coitum, respectively. Treatment at 200 mg/kg bw/day resulted in statistically significantly lower body weight gains on Days 12 and 15 post-coitum. Food consumption was statistically significantly lower from Day 6 to Day 12 post-coitum. As these changes recovered during the remainder of the treatment period, they were considered non-adverse. At 200 and 600 mg/kg bw/day, relative liver weights were statistically significantly increased with 6% and 13% when compared to controls, respectively. Since there is no correlation at macroscopic or microscopic examination, the effect on liver weight was not considered toxicologically relevant. Weight gain corrected for gravid uterus was unaffected and no toxicologically relevant clinical signs, macroscopic or microscopic alterations were noted. No maternal toxicity was observed in the 60 mg/kg bw/day group. Regarding developmental toxicity, no toxicologically relevant effects on the fetal weight, changes in sex ratio, litter size and litter weight were observed. External, skeletal and visceral malformations were observed in single fetuses. All these effects were considered to have occurred by chance and/or at low incidences and/or in the absence of a dose-related incidence, and thus, these effects were considered not to be of toxicological relevance.

No developmental toxicity was observed in the 60, 200 and 600 mg/kg bw/day groups. Based on the results in this prenatal developmental toxicity study the maternal No Observed Adverse Effect Level (NOAEL) for the source substance was established at 200 mg/kg bw/day. The offspring and developmental NOAEL was established at 600 mg/kg bw/day, the highest dose tested.

Justification for classification or non-classification

The available data on toxicity to reproduction does not meet the classification criteria according to Regulation (EC) 1272/2008. However, as no sub-chronic repeated dose toxicity study is available, the conclusion for classification is ´data lacking`.

Additional information