Methylidynetri-p-phenylene triisocyanate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Remarks:

other: subacute study

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: OECD TG 412

GLP compliance:

yes (incl. QA statement)

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

nose only

Vehicle:

other: dry conditioned air

Details on mating procedure:

not applicable because it is a subacute study

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

6 hours per day

Remarks:

Doses / Concentrations:
0, 0.47, 3.9, 34.9 mg/m³
Basis:
other: gravimetric concentrations

No. of animals per sex per dose:

5

Control animals:

other: yes: dry conditioned air

Dose descriptor:

NOEC

Effect level:

34.9 mg/m³ air (analytical)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: adverse effects on reproductive organs or tissues

Reproductive effects observed:

not specified

Conclusions:

No adverse effects on reproductive organs or tissues were observed in a subacute inhalation study with rats at 34.9 mg/m³.

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

34.9 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

Based on the subacute inhalation study, there is no indication of a reproductive toxicity potential.

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a subacute inhalation toxicity study (OECD TG 412) male/female Wistar rats per dose group were nose-only exposed for 4 weeks (6 hours /day, 5 days/week) to the aerosolized substance. The mean actual concentrations (gravimetric) were 0.47, 3.9 and 34.9 mg Triphenylmethane-4,4',4''-triisocyanate/m³. No adverse effects on reproductive organs or tissues were observed at 34.9 mg/m³.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Quality of whole database:

Neither a developmental study (OECD TG 414) nor a testing proposal for such a study are available. Data waiver is claimed.

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The toxicological database for inhaled Triphenylmethane-4,4',4''-triisocyanate demonstrates consistently that toxicity is associated only with the portal of entry (respiratory tract). Acute and subacute inhalation studies with Triphenylmethane-4,4',4''-triisocyanate show toxicity confined to the respiratory tract. In general, the toxicological effects observed resulting from inhalation exposure of Triphenylmethane-4,4',4''-triisocyanate, reveal a pattern characteristic for local irritation and its sequelae with lack of systemic toxicity. This mode of action is in line with other diisocyanates and wholly consistent with the chemical reactivity of the isocyanate functional group. Developmental toxicity studies with other diisocyanates (MDI, TDI and HDI) have shown no evidence of any diisocyanate being a developmental toxicant. Mild effects on the foetuses seen with high level exposures to these diisocyanates are considered secondary to the toxicity to the respiratory system of the exposed dams. Therefore, it is proposed that, based on the similar major mode of action as port of entry toxicant, the lack of developmental toxicity seen with MDI, TDI and HDI applies equally to Triphenylmethane-4,4',4''-triisocyanate (many-to-one read-across). Therefore, based on read across there is no indication of a developmental toxicity potential. Protection against respiratory tract toxicity will protect against any secondary effects. In addition, the need to adopt risk management measures to protect against the sensitising potential of these chemicals provides enhanced safeguards. Taking all these points into account (weight of evidence), it is concluded that developmental toxicity is not an endpoint of concern for Triphenylmethane-4,4',4''-triisocyanate.