2-methyl-m-phenylene diisocyanate

Endpoint summary

Description of key information

2,6-toluene diisocyanate (CAS no 91-08-7) is likely to be non hazardous by oral route of exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.4.

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4.

GLP compliance:

no

Test type:

standard acute method

Specific details on test material used for the study:

Name: 2,6-toluene diisocyanate
Molecular Formula:C9H6N2O2
Molecular Weight: 174.1584 g/mole
SMILES:Cc1c(N=C=O)cccc1N=C=O

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

No data available

Doses:

No data available

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 672.1 mg/kg bw

Based on:

test mat.

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c") and("d" and(not "e")) ) and "f") and "g") and("h" and(not "i")) ) and("j" and "k") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Acylation AND Acylation >> Isocyanates and Isothiocyanates AND Acylation >> Isocyanates and Isothiocyanates >> Isocyanates by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Acylation AND Acylation >> (Tio)carbamoylation of protein nucleophiles AND Acylation >> (Tio)carbamoylation of protein nucleophiles >> Isothiocyanates, Isocyanates AND AN2 AND AN2 >> Direct carbamoylation of protein amines AND AN2 >> Direct carbamoylation of protein amines >> Isocyanates and Diisocyanates by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Acylation AND Acylation >> Isocyanates and Related Chemicals AND Acylation >> Isocyanates and Related Chemicals >> Isocyanates by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Non binder, MW>500 OR Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as Alkyl arenes AND Aryl AND Isocyanate by Organic Functional groups

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as Alkene OR Allyl OR Benzyl by Organic Functional groups

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.14

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.74

Interpretation of results:

other: not classified

Conclusions:

estimated LD50 was considered to be 3672.1 mg/kg bw when Fischer 344 male and female rats were treated with 2,6-toluene diisocyanate orally.

Executive summary:

Acute oral toxicity was estimated using QSAR Toolbox 3.4 (2016) in Fischer 344 male and female rats by using 2,6-toluene diisocyanate in the concentration of 3672.1 mg/kg bw orally. No mortality was observed in treated male and female rats. Therefore, estimated LD50 was considered to be 3672.1 mg/kg bw when Fischer 344 male and female rats were treated with 2,6-toluene diisocyanate orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 672.1 mg/kg bw

Quality of whole database:

Data is klimisch 2 and from QSAR Toolbox 3.4 (2016)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity 

Based on the data available for target 2,6-toluene diisocyanate (CAS no 91-08-7) and its read across Toluene diisocyanate (CAS no 26471-62-5) for acute oral toxicity is summarized below

Based on the prediction done by using QSAR Toolbox 3.4 (2016), acute oral toxicity was estimated in Fischer 344 male and female rats by using 2,6-toluene diisocyanate in the concentration of 3672.1 mg/kg bw orally. No mortality was observed in treated male and female rats. Therefore, estimated LD50 was considered to be 3672.1 mg/kg bw when Fischer 344 male and female rats were treated with 2,6-toluene diisocyanate orally.

In a study conducted by J-CHECK (2012) for read across, acute oral toxicity was evaluated in Crj:CD (SD) male and female rats by using Toluene diisocyanate in the concentration of 0 and 2000 mg/kg bw orally by gavage in corn oil and observed for 14 days. No effect on survival of treated male and female rats was observed as compared to control. In addition, no effect on body weight and gross pathology of treated male and female rats were observed as compared to control. Therefore, LD50 was considered to be > 2000 mg/kg bw when Crj:CD (SD) male and female rats were treated with Toluene diisocyanate orally by gavage.

In a study given by National Toxicology Program (1986) for read across, single dose acute oral toxicity was evaluated in F344/N male and female rats were treated with Toluene diisocyanate in the concentration of 2,150, 3,160, 4,640, 6,810, 10,000 and 14,700 mg/kg bw in corn oil orally by gavage. all male and female rats were died on day 2 at 10000 and 14700 mg/kg bw, 3 male rats were died on day 4 and 5 at 6810 mg/kg bw, 2 male died on day 2 and 10 and 3 female rats died on day 2 at 4640 mg/kg bw, 2 male died on day 13 and 14, and 3 female on day 3 at 3160 mg/kg bw and No effect on survival of female rats at 2150 mg/kg bw and 3 male died on day 5 and 9. Death was preceded by labored breathing, inactivity, and diarrhea when treated with 10000 and 14700 mg/kg bw. Decrease in body weight was observed in 10000 mg/kg bw treated male and female rats. In addition, White, crystalline material was found in the stomach and dark red lungs were observed in treated rats. Therefore, LD50 was considered to be 2150 mg/kg bw for male and > 2150 mg/kg bw for female when F344/N male and female rats were treated with Toluene diisocyanate orally by gavage.

In the above similar source, B6C3F1 male and female mice were also evaluated by using Toluene diisocyanate in the concentration of 2,150, 3,160, 4,640, 6,810 and 10,000 mg/kg for male and 3,160, 4,640, 6,810 and 10,000 mg/kg for female mice in corn oil orally by gavage. All male and female mice were died on day 1 and 2 at 10000 mg/kg bw, 1 female mice were died on day 1 and 2 at 6810 mg/kg bw, 1 male died on day 8 and 4 female mice died on day 5 at 4640 mg/kg bw, 2 male died on day 13 and 14, and 3 female on day 3 at 3160 mg/kg bw and No effect on survival of male and female mice at 3160 mg/kg bw was observed. In addition, White, crystalline material in the stomach was observed in treated mice. Therefore, LD50 was considered to be 4640 mg/kg bw for male and 6810 mg/kg bw for female when B6C3F1 male and female mice were treated with Toluene diisocyanate orally by gavage.

Thus, based on the weight of evidence for target 2,6-toluene diisocyanate (CAS no 91-08-7) and its read across Toluene diisocyanate (CAS no 26471-62-5) is likely to be non hazardous by oral route of exposure.

Justification for selection of acute toxicity – oral endpoint

estimated LD50 was considered to be 3672.1 mg/kg bw when Fischer 344 male and female rats were treated with 2,6-toluene diisocyanate orally.

Justification for classification or non-classification

Based on the weight of evidence for target 2,6-toluene diisocyanate (CAS no 91-08-7) and its read across Toluene diisocyanate (CAS no 26471-62-5) is likely to be non hazardous by oral route of exposure.