Trisodium 5-[[4-chloro-6-(ethylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(1-sulphonato-2-naphthyl)azo]naphthalene-2,7-disulphonate

Endpoint summary

Description of key information

FAT 40147 is neither a skin nor an eye irritant.

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

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted May 12, 1981

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

Company code: FAT 40'147/E
Batch No.: EN 94'066.32
Appearance: powder
Purity: 83.3 %
Stability of the test Compound: until October 1988
pH-value: 7.9 (1 g/L water)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Number and sex of animals used: 3 females
- Initial age: 12 - 14 weeks
- Initial body weight range: 2020-2410 g
- Individual identification: numbered ear tags; The cages were marked with sex, animal No., GU-Project No. and the company code of the test article.
- Husbandry: Animals were housed individually in metal cages. The animal room was air conditioned: temperature 20±3° C, relative humidity 30-70 %; 12 hours light/day, approximately 15 air changes/h.
- Diet and water: Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), and water were provided ad libitum.
- Euthanasia: At the end of the observation period, the animals were sacrificed by intravenous injection of hypnotic T61 (Hoechst).

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

- Application of the Substance:
A gauze patch bearing 0.5 g of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape (ISOPLAST AG, CH-5200 Brugg). The substance was water
moistened before application. Exposure duration was 4 hours.

- Study evaluation:
- Scoring of symptoms and local reactions: After removal of the dressings the skin reaction was assessed on the basis of an evaluation scheme, after 1, 24, 48, 72 hours and during the following
observation period.
- Mode of calculation: The index of primary cutaneous irritation was calculated as follows:
- the scores obtained for erythema and oedema at 1 hour, 24, 48 and 72 hours after removal of the patch, on the 3 rabbits examined, are summed up
- the sums of total oedema and erythema were divided by 12, when all the animals survived.
- the score obtained is defined as the "index of primary cutaneous irritation".
- Symptoms: daily (a.m. and p.m. on working days, once daily on weekends and holidays).
- Body weight: at beginning of acclimatization and end of test.
- Mortality: daily a.m.and p.m., once daily on weekends and holidays.

Interpretation of the primary-irritation index:
< 0.5 : non irritant
0.6 - 3.0 : slightly irritant
3.1 - 5.0 : irritant
5.1 - 8.0 : severely irritant

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Remarks on result:

other: Due to intensive staining by the test substance a scoring of the erythema values at 24 hours was not possible

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

other: INDEX of skin irritation

Basis:

mean

Time point:

other: 1/24/48/72 h

Score:

0.17

Max. score:

8

Irritant / corrosive response data:

Due to intensive red staining by the test substance a scoring of the erythema values was not possible.

The dermal irritation was evaluated after the score for oedema formation only. The animals had recovered at the end of the observation period of 7 days.

Other effects:

The animals showed a normal body weight development.

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40147/E can be considered as not a skin irritant.

Executive summary:

The skin irritation potential of the test substance was evaluated according to OECD Guideline 404. The test was performed on 3 female adult New Zealand White rabbits between the age of 12 - 14 weeks and weighing 2.020 to 2.410 kgs. Not less than 24 hours before treatment on the back of the experimental animal an area was shaven of at least 6 sq. cm,- by means of an electric clipper. A gauze patch bearing 0.5 g of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape (ISOPLAST AG, CH-5200 Brugg). Exposure duration was 4 hours. The skin reaction was appraised after 1, 24, 48, 72 hours and 7 days upon removal of the dressings. The score obtained is defined as the "index of primary cutaneous irritation". Due to intensive red staining by the test substance a scoring of the erythema values was not possible. The dermal irritation was evaluated after the score for oedema formation only. The animals had recovered at the end of the observation period of 7 days. Index of skin irritation was calculated to be 2.33. However, the scores for erythema and edema do not meet the classification criteria proposed by CLP (Regulation 1272/2008). Hence, the substance FAT 40147/E can be considered as not a skin irritant.

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:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

None

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted May 12, 1981

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

yes

Specific details on test material used for the study:

Company code: FAT 40'147/E
Batch No.: EN 94'066.32
Purity: 83.3 %
Appearance: powder
Stability of the test compound: until October 1988
pH-value: 7.9 (1g/l water)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
Number and sex of animals used: 3 males
Initial age range: 12 - 14 weeks
Initial body weight range: 2150-2370 G
Individual identification: numbered ear tags. The cages were marked with animal No.and sex, the GU-Project No.and the company code of the test article.
Husbandry: Animals were housed individually in metal cages. The animal room was air conditioned: temperature 20±3° C, relative humidity 30-70 %; 12 hours light/day, approximately 15 air changes/h.
Diet and water: Rabbit food NAFAG No.814 Tox, NAFAG AG, Gossau, SG (Switzerland), and water were provided ad libitum.
Euthanasia: At the end of the observation period, the animals were killed by the intravenous injection of hypnotic T61 (Hoechst).

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and served as a control.

Amount / concentration applied:

0.1 g

Observation period (in vivo):

10 days

Number of animals or in vitro replicates:

3 males

Details on study design:

Test Procedure:
0.1 g of the test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material. The left eye remained untreated and served as the control.

Scoring and assessment of local reactions:
The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period by means of a slit-lamp. The ocular irritation scores were evaluated.
The irritating and/or corrosive potential of the test article (theoretical range: non irritant - extremely irritant) was assessed on the basis of the maximum irritant effect observed
- in one or several of the ocular tissues (conjunctiva, iris, cornea), observed over the range of observation time
- in one or more animals
and taking into account the reversibility of the effect.

Symptoms: daily a.m.and p.m. on working days,once daily on weekends and holidays
Body weight: at begin of the acclimatization and at end of test
Mortality: daily a.m.and p.m. on working days,once daily on weekends and holidays

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Due to intensive red staining by the test substance, scoring for corneal opacity was not possible till 72 hours

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Max. score:

3

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: Due to intensive red staining by the test substance, scoring for corneal opacity was not possible till 7 days (animal no. 1), 48 hours (animal no. 2) and 72 hours (animal no. 3)

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

The animals had recovered at the end of the observation period of 10 days.

Other effects:

The animals showed a normal body weight development.

Due to intensive red staining, scoring for corneal opacity and conjunctival redness was not possible at certain observation time points (see remarks in the 'Results of in vivo study' for details).

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40147/E can be considered as not an eye irritant.

Executive summary:

The eye irritation potential of the test substance was evaluated in a study conducted according to OECD Guideline 405. The test was performed on 3 male New Zealand White rabbits. The test material in an amount of 0.1 g was inserted into the conjunctival sac of the right eye of the rabbits and the lidsthen held together for about one second in order to prevent loss of the test material. The left eye was not treated and served as an untreated control.The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period by means of a slit-lamp. Due to intensive red staining, scoring for corneal opacity and conjunctival redness was not possible at certain observation time points.

A slight irritation with conjunctival redness and chemosis was observed. The animals were free of findings by the day 10. The mean score for chemosis was calculated to be 1.8, with two animals having a mean score of 1.7 and one animal having a mean score of 2. Hence, the scores do not meet the classification criteria sert forth by CLP (Regulation 1272/2008). Based on the above findings, the test substance FAT 40147/E can be considered as not an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Four in vivo studies to evaluate the skin irritation potential of FAT 40147 are available.

In a key study (1984), the skin irritation potential of the test substance was evaluated according to OECD Guideline 404. The test was performed on 3 female adult New Zealand White rabbits between the age of 12 - 14 weeks and weighing 2.020 to 2.410 kgs. Not less than 24 hours before treatment on the back of the experimental animal an area was shaven of at least 6 sq. cm,- by means of an electric clipper. A gauze patch bearing 0.5 g of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape (ISOPLAST AG, CH-5200 Brugg). Exposure duration was 4 hours. The skin reaction was appraised after 1, 24, 48, 72 hours and 7 days upon removal of the dressings. The score obtained is defined as the "index of primary cutaneous irritation". Due to intensive red staining by the test substance a scoring of the erythema values was not possible. The dermal irritation was evaluated after the score for oedema formation only. The animals had recovered at the end of the observation period of 7 days. Index of skin irritation was calculated to be 2.33. However, the scores for erythema and edema do not meet the classification criteria proposed by CLP (Regulation 1272/2008). Hence, the substance FAT 40147/E can be considered as not a skin irritant.

Similarly, three other studies conducted with FAT 40147/B (1981), FAT 40147/C (1982) and FAT 40147/D (1982) also support the conclusion that the substance is not a skin irritant.

Eye irritation:

Three studies to evaluate the eye irritation potential of FAT 40147 are available.

In a key study, the eye irritation potential of the test substance was evaluated in a study conducted according to OECD Guideline 405. The test was performed on 3 male New Zealand White rabbits. The test material in an amount of 0.1 g was inserted into the conjunctival sac of the right eye of the rabbits and the lidsthen held together for about one second in order to prevent loss of the test material. The left eye was not treated and served as an untreated control.The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period by means of a slit-lamp. Due to intensive red staining, scoring for corneal opacity and conjunctival redness was not possible at certain observation time points. A slight irritation with conjunctival redness and chemosis was observed. The animals were free of findings by the day 10. The mean score for chemosis was calculated to be 1.8, with two animals having a mean score of 1.7 and one animal having a mean score of 2. Hence, the scores do not meet the classification criteria sert forth by CLP (Regulation 1272/2008). Based on the above findings, the test substance FAT 40147/E can be considered as not an eye irritant.

Similarly, two other studies conducted with FAT 40147/B (1981) and FAT 40147/C (1982) also support the conclusion that the substance is not a eye irritant.

Justification for classification or non-classification

Based on the available studies, FAT 40147 does not need to be classified according to CLP (Regulation 1272/2008) criteria.