Benzoic acid, 2,3,4,5-tetrachloro-6-cyano-, methyl ester, reaction products with p-phenylenediamine and sodium methoxide

Endpoint summary

Description of key information

- Skin: according to AFDO guidelines, prior GLP, six rabbits (3/sex/dose), 24h occlusive treatment, not irritating

- Eye: according to Fed. Reg. 38 No. 187 §1500.42, prior GLP, instillation into one eye, rinsed after 30s in 3/6 rabbits, not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

no data on purity; occlusive testing in 6 animals for 24 h; missing 48 h reading; no information on environmental conditions

Qualifier:

according to guideline

Guideline:

other: Fed. Reg. 38 No. 187 § 1500.42

Deviations:

no

Principles of method if other than guideline:

- Limitations: no data on purity; occlusive testing in 6 animals for 24 hrs; missing 48 h reading, no information on environmental conditions

GLP compliance:

no

Specific details on test material used for the study:

- Analytical purity: no data

Species:

rabbit

Strain:

other: Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.5 - 2 kg
- Housing: separately
- Diet (e.g. ad libitum): NAFAG, Gossau SG, rabbit food; ad lib.
- Water (e.g. ad libitum): unspecified; ad lib.

ENVIRONMENTAL CONDITIONS
not reported

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: polyethylene glycol trituration (PEG 400)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 50%

Duration of treatment / exposure:

24 h

Observation period:

72 h

Number of animals:

6 (3 males and 3 females)

Details on study design:

TEST SITE
- Area of exposure: 2.5*2.5 cm on back or flanks
- Type of wrap if used: gauze patch covered with plastic film

REMOVAL OF TEST SUBSTANCE
not reported

SCORING SYSTEM: OECD Draize Scoring System

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 & 72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 & 72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Purity not reported

Qualifier:

according to guideline

Guideline:

other: Fed. Reg. 38 No. 187 §1500.42

Deviations:

yes

Principles of method if other than guideline:

- Limitations: 3 animals were rinsed after 30 s, 3 animals were not rinsed; Purity not reported

GLP compliance:

no

Specific details on test material used for the study:

- Physical state: solid
- Analytical purity: no data

Species:

rabbit

Strain:

other: Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: separately in V2A wire cages
- Diet (e.g. ad libitum): NAFAG, Gossau SG, CH; ad lib.
- Water (e.g. ad libitum): unspecified; ad lib.
- Acclimation period:

ENVIRONMENTAL CONDITIONS
not reported

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

3 animals: without rinsing
3 animals: rinsed after 30 s

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

in total 6

Details on study design:

REMOVAL OF TEST SUBSTANCE
3 animals: without rinsing
3 animals: rinsed after 30 s

SCORING SYSTEM: OECD Draize Scoring System

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals (rinsed or not rinsed)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals (rinsed or not rinsed)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals (rinsed or not rinsed)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Criteria for the valuation of chemosis and discharge effects were given in the report, but no detailed results were presented. It is assumed that the parameter "conjunctivae" covers conjunctivae redness and chemosis in combination.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

In the course of the key study (according AFDO guideline, prior GLP), 0.5g of the test material dissolved in PEG were applied to intact and scarified skin of 3 male and 3 female Russian rabbits for 24h under occlusive conditions. Skin reactions were evaluated after removal of the patch and after 72h. The substance did not provoke erythema or edema; the irritation index was therefore 0.

 

The skin irritation potential was evaluated in two other studies in rabbits. 0.5g of the test material were applied to intact and scarified skin of 6 rabbits for 24h under occlusive conditions. Skin reactions were scored after 24h and after 72h. No effects were seen in the one of these studies (BASF, 1975). In the other study (BASF, 1976, disregarded), the material caused slight erythema and edema which were reversible after 72h. However, in the latter study, the purity of the substance was below 80%. Therefore, the effects observed may originate from solvents or impurities.

 

As a result, the test substance is regarded not irritating to skin.

 

Eye:

The eye irritation potential was determined by instillation of 0.1g of the test substance into Russian rabbits eyes (one treated eye, untreated served as control). At three of the six animals the treated eyes were rinsed 30 sec after instillation. Scoring of the reaction was carried out 24h, 48h and 72h after treatment; neither chemosis nor effects on conjunctiva were observed up to 7d after treatment.

 

The second and third study were performed in a comparable manner in rabbits: 0.1g undiluted test material was instilled in one eye, 3/6 eyes were rinsed 30sec after treatment, scoring of treated and untreated eyes 24h, 48h and 72h after instillation and observation for 7d. In the course of one study (BASF, 1975), the material did not provoke any reaction into the rabbit eyes. Application of the compound in the other study (BASF, 1976, disregarded) caused slight effects on iris and conjunctiva as well as chemosis. All symptoms were reversible within the post observation period. However, the purity of the substance was below 80%. Therefore, the effects observed may originate from solvents or impurities.

 

As a result, the test substance is regarded not irritating to eyes.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.