Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda

Endpoint summary

Description of key information

Skin: similar to OECD 404 guideline study, rabbits, exposure for 4h under occlusive dressing: slightly irritating but no classification is required.
Eye: similar to OECD 405 guideline study, rabbits, persistence of eyes damages at the end of the observation period (7 days).
Respiratory tract: signs of irritation of the respiratory tract in the acute inhalation study (see 7.2.2 Ac. inhalation tox V1 2013 CitoxLab) and reporting of respiratory irritation cases in Human (see 7.10.5 exposure related observation in humans: manufacturing plant)

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:

from 11 March 1994 to 29 June 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is sufficiently documented. No certificate of analysis is available.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

other: New Zealand Albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Source: Animals were received from Ace Animals on 1/18, 2/15 and 2/22/94.
- Age at study initiation: The animals were born the week of 10/24 through 12/12/93.
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: The animals were housed 1/cage in suspended cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet # 5321)
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: three days

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): No data on temperature but the animal room was temperature controlled.
- Humidity (%): data not available
- Air changes (per hr): data not available
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: data not available

Type of coverage:

occlusive

Preparation of test site:

other: clipped free of hair, intact or abraded

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Test material: Amount applied: 0.5 g/site (dry weight of the test article). The test article was moistened with distilled water (made pasty) after application .
pH: data not available

Duration of treatment / exposure:

4 hour(s)

Observation period:

At 3 min, 1, 4, 24, 48, 72 hours and on day 7 after patch removal

Number of animals:

3

Details on study design:

TEST SITE:
- Area of exposure: disk of ca. 2-3 cm of diameter
- % coverage: data not available
- Type of wrap if used: two 2.5 cm square gauze patch which were secured with adhesive tape. The torso was wrapped with plastic and secured with adhesive tape.

REMOVAL OF TEST SUBSTANCE:
- Washing: any residual test article was washed off with distilled water prior to dermal observations.
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to Draize
- Erythema and Eschar Formation:
No erythema -> 0
Very slight erythema (barely perceptible) ->1
Well defined erythema -> 2
Moderate to severe erythema -> 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema -> 4

- Oedema Formation:
No oedema -> 0
Very slight oedema (barely perceptible) -> 1
Slight oedema (edges of area well defined by definite raising) -> 2
Moderate oedema (raised approximately 1 mm) -> 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure) -> 4

- Primary Dermal Irritation Index = (Sum of individual Erythema scores + Sum of individual Edema scores) / 12

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: intact skin. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.33 and 1.7.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: intact skin. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.33 and 1.0.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

1.17

Max. score:

8

Reversibility:

fully reversible within: 72 hours or 7 days

Remarks on result:

other: scarified and intact skin

Irritant / corrosive response data:

Erythema, absent at 3 minutes post dose, was absent to slight at one and four hours. At 24 and 48 hours after patch removal, erythema was absent to well defined. At 72 hours erythema was absent to slight and absent on day 7. Edema, absent at 3 minutes post dose, was absent to slight at one and four hours. At 24 hours after patch removal, edema was absent to well defined. Edema was absent to slight at 48 hours and absent at 72 hours and on day 7. The modified primary irritation index is 1.17.

SEE INDIVIDUAL SCORES IN TABLE 1 BELOW

Other effects:

There were no signs of systemic toxicity noted during the observation period.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema		Edema
	Max. score: 4		Max. score: 4
	normal	scarified	normal	scarified
3 min	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
1 hr	0 / 0 / 1	1 / 0 / 0	0 / 0 / 1	0 / 0 / 0
4 hrs	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 1
24 hrs	0 / 1 / 2	1 / 0 / 2	0 / 1 / 2	1 / 0 / 2
48 hrs	0 / 0 / 2	0 / 0 / 2	0 / 0 / 1	1 / 0 / 1
72 hrs	0 / 0 / 1a	0 / 0 / 1a	0 / 0 / 0	0 / 0 / 0
7 days	0 / 0 /0f	0 / 0 /0f	0 / 0 / 0	-
Average 24h, 72h	0.0 /0.33/ 1.7	0.33/ 0.0 /1.7	0.0 /0.33/ 1.0	0.66 / 0.0 / 1.0
Reversibility*)	c.	c.	c.	c.
Average time (unit) for reversion	7 days	7 days	72 h	72 h

 

*) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

a = skin appeared dry

f = flaking skin

Interpretation of results:

slightly irritating

Remarks:

Migrated information The test chemical was considered as slightly irritating and no classification according to EU criteria is required. Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the test item was slightly irritant when applied topically to rabbits. However, according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda should not be classified as irritating to the skin.

Executive summary:

 In a primary dermal irritation study (1994), New Zealand Albino rabbits (3 animals) were dermally exposed to 0.5 g of undiluted test article. Intact and abraded test sites were covered with an occlusive dressing for 4 hours. Skin sites were then scored for erythema and oedema 3 min, 1 hour, 4, 24, 48, 72 hours and day 7 after patch removal. Irritation was scored by the method of Draize.

 

Erythema, absent at 3 minutes post dose, was absent to slight at one and four hours. At 24 and 48 hours after patch removal, erythema was absent to well defined. At 72 hours erythema was absent to slight and absent on day 7. Edema, absent at 3 minutes post dose, was absent to slight at one and four hours. At 24 hours after patch removal, edema was absent to well defined. Edema was absent to slight at 48 hours and absent at 72 hours and on day 7.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.33 and 1.7 for erythema and 0.0, 0.33 and 1.0 for edema. Similar effects were observed with abraded skin. The modified primary irritation index is 1.17.

 

Under the experimental conditions of this study, the test item was slightly irritant when applied topically to rabbits. Based on these results, the test item reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is not classified as irritating to the skin according to Annex VI of the Directive 67/548/CEE and to EU Regulation 1272/2008 (CLP).

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:

from 11 March 1994 to 29 June 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is sufficiently documented. No certificate of analysis is available.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

other: New Zealand Albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS:
- Source: Animals were received from Ace Animals on 1/18, 2/15 and 2/22/94.
- Age at study initiation: The animals were born the week of 10/24 through 12/12/93.
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: The animals were housed 1/cage in suspended cages. Bedding was placed beneath the cages and changed at least three times/week.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet # 5321)
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: three days

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): No data on temperature but the animal room was temperature controlled.
- Humidity (%): data not available
- Air changes (per hr): data not available
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: data not available

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL:
- Amount applied (volume or weight with unit): 0.1 ml equivalent of test material introduced into the conjunctival sac of the each eye
- Concentration (if solution): not applicable
- pH: no applicable

VEHICLE: /

Duration of treatment / exposure:

Single conjunctival instillation

Observation period (in vivo):

1 hour, and days 1, 2, 3 and 7 after the instillation

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing : 20-30 seconds after instillation of the test article, the left eye of each rabbit was flushed for one minute with lukewarm water. The right eye of each animal remained unwashed.


SCORING SYSTEM: The eyes were examined and scored by the Draize technique at 1 hour post dose and again on days 1, 2, 3 and 7 post dose.

TOOL USED TO ASSESS SCORE: data not available

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 1.33 - <= 2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Unwashed: Mean scores calculated for each animal over 24, 48 and 72 hours were 2.0, 1.33 and 1.33 for corneal opacity.

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Remarks:

at day 7

Remarks on result:

other: Unwashed: Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 1.0 and 1.0 for iris lesions.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 2 - <= 2.7

Max. score:

3

Reversibility:

not reversible

Remarks:

at day 7 for 1 animals

Remarks on result:

other: Unwashed: Mean scores calculated for each animal over 24, 48 and 72 hours were 2.7, 2.0 and 2.0 for redness of the conjunctiva

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 2.33 - <= 3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Unwashed: Mean scores calculated for each animal over 24, 48 and 72 hours were 3.0, 2.33 and 3.0 for chemosis.

Irritant / corrosive response data:

Unwashed: Corneal opacity, noted in 3/3 eyes, persisted up to day 7. Iritis, noted in 3/3 eyes, cleared by day 7. Moderate conjunctival irritation, noted in 3/3 eyes, persisted up to day 7 in one eye and improved to slight in two eyes.
Washed: Corneal opacity was noted in two eyes on day 7. Iritis, noted in 3/3 eyes, persisted up to day 7 in one eye. Moderate conjunctival irritation, noted in 3/3 eyes, persisted up to day 7 in one eye, cleared in one eye and improved to slight in the third eye.

Other effects:

There were no signs of systemic toxicity noted during the observation period.

Result Table: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

 

Unwashed right eye:

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	2/0h/0h	1/1/1	2/2/2	3/3/3
24 h	2/0h/0h	1/1/1	2/2/2	3/3/3
48 h	2/2/2	1/1/1	3/2/2	3/2/3
72 h	2/2/2	1/1/1	3/2/2	3/2/3
Average 24h, 48h, 72h	2/1.33/1.33	1/1/1	2.7/2/2	3/2.33/3
Reversibility*)	n.	c.	n.c.	n.
Average time (unit) for reversion	-	Day 7	Day 7 (2/3 eyes)	-

 

*) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

         

h: lack of normal luster

 

Washed left eye:

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0	0/0/0	1/1/2	2/3/3
24 h	0h/0h/0h	0/1/0	2/2/2	2/3/3
48 h	0h/0h/0h	1/1/0	3/2/2	2/3/3
72 h	0h/0h/0h	1/1/0	3/2/2	2/3/3
Average 24h, 48h, 72h	0/0/0	0.66/1/0	2.66/2/2	2/3/3
Reversibility*)	n.c. (score :2 in 2 animals at day 7)	n.c. (score :1 in 1 animal at day 7)	n.c. (score : 1 and 2 in 2 animals at day 7)	n.c. (score :2 in 1 animal at day 7)
Average time (unit) for reversion	-	-	-	-

 

*) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

         

h: lack of normal luster

Interpretation of results:

highly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the test item was found severely irritating to the eye of rabbit. Based on these results, the test item reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is classified Xi, R 41, risk of serious damage to eyes, according to Annex VI of the Directive 67/548/CEE, and Eye Damage Cat 1, H318 according to EU Regulation 1272/2008 (CLP), considering the persistence of eye damages at the end of the observation period (7 days).

Executive summary:

In a primary eye irritation study (1994), 0.1 ml equivalent of the test article was instilled into the conjunctival sac of each eye of New Zealand Albino rabbits (3 animals). 20-30 seconds after instillation of the test article, the left eye of each rabbit was flushed for one minute with lukewarm water. The right eye of each animal remained unwashed. Animals were then observed for 7 days. Irritation was scored by the method of Draize.

For unwashed eyes : Corneal opacity, noted in 3/3 eyes, persisted up to day 7. Iritis, noted in 3/3 eyes, cleared by day 7. Moderate conjunctival irritation, noted in 3/3 eyes, persisted up to day 7 in one eye and improved to slight in two eyes.

Mean scores calculated for each animal over 24, 48 and 72 hours were 2.0, 1.33 and 1.33 for corneal opacity; 1.0, 1.0 and 1.0 for iris lesions; 2.7, 2.0 and 2.0 for redness of the conjunctiva and 3.0, 2.33 and 3.0 for chemosis.

For washed eyes: Corneal opacity was noted in two eyes on day 7. Iritis, noted in 3/3 eyes, persisted up to day 7 in one eye. Moderate conjunctival irritation, noted in 3/3 eyes, persisted up to day 7 in one eye, cleared in one eye and improved to slight in the third eye.

Under the experimental conditions of this study, the test item was found severely irritating to the eye of rabbit. Based on these results, the test item reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is classified Xi, R 41, risk of serious damage to eyes, according to Annex VI of the Directive 67/548/CEE and Eye Damage, Cat 1, H318 according to EU Regulation 1272/2008 (CLP), considering the persistence of eyes damages at the end of the observation period (7 days).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

One Klimisch score 2 study was available for dermal irritation and was used as a key study:

In this primary dermal irritation study (1994), New Zealand Albino rabbits (3 animals) were dermally exposed to 0.5 g of undiluted test article. Intact and abraded test sites were covered with an occlusive dressing for 4 hours. Skin sites were then scored for erythema and oedema 3 min, 1 hour, 4, 24, 48, 72 hours and day 7 after patch removal. Irritation was scored by the method of Draize. In the intact skin, erythema, absent at 3 minutes post dose, was absent to slight at one and four hours. At 24 and 48 hours after patch removal, erythema was absent to well defined. At 72 hours erythema was absent to slight and absent on day 7. Edema, absent at 3 minutes post dose, was absent to slight at one and four hours. At 24 hours after patch removal, edema was absent to well defined. Edema was absent to slight at 48 hours and absent at 72 hours and on day 7. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.33 and 1.7 for erythema and 0.0, 0.33 and 1.0 for edema. Similar effects were observed in abraded skin. The modified primary irritation index is 1.17. Under the experimental conditions of this study, the test item was slightly irritant when applied topically to rabbits.

One Klimisch score 2 study was available for eye irritation and was used as a key study:

In this primary eye irritation study (1994), 0.1 ml of test article was instilled into the conjunctival sac of each eye of New Zealand Albino rabbits (3 animals). 20-30 seconds after instillation of the test article, the left eye of each rabbit was flushed for one minute with lukewarm water. The right eye of each animal remained unwashed. Animals were then observed for 7 days. Irritation was scored by the method of Draize. For washed eyes : Corneal opacity, noted in 3/3 eyes, persisted up to day 7. Iritis, noted in 3/3 eyes, cleared by day 7. Moderate conjunctival irritation, noted in 3/3 eyes, persisted up to day 7 in one eye and improved to slight in two eyes. Mean scores calculated for each animal over 24, 48 and 72 hours were 2.0, 1.33 and 1.33 for corneal opacity; 1.0, 1.0 and 1.0 for iris lesions; 2.7, 2.0 and 2.0 for redness of the conjunctiva and 3.0, 2.33 and 3.0 for chemosis. For washed eyes: Corneal opacity was noted in two eyes on day 7. Iritis, noted in 3/3 eyes, persisted up to day 7 in one eye. Moderate conjunctival irritation, noted in 3/3 eyes, persisted up to day 7 in one eye, cleared in one eye and improved to slight in the third eye. Under the experimental conditions of this study, the test item was found severely irritating to the eye of rabbit.

Irritant effects of the respiratory tract were observed in the acute inhalation study (2013) performed in rats with an aerosol of Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda. Indeed during the exposure and short at the end of exposure laboured, gasping and/or noisy respiration, respiratory rate increased, sneezing, were observed in the rats exposed to concentrations from 0.51 to 5.14 mg/mL for a period of 4h. During the 14 days observation period, gasping respiration, sneezing were observed in the surviving animals.

At necropsy, dark/red discoloration of the non-collapsed lungs and white foamy material in the trachea were seen in all found dead animals (n=8) receiving 5.07 and 5.14 mg/L).

The respiratory irritant effects associated with the inhalation of the registered substance were also recorded in workers exposed to the registered substance in the manufacturing plant.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available (similar to OECD 404, GLP compliant)

Justification for selection of eye irritation endpoint:
Study performed according to protocol similar to OECD 405 Guideline (Klimisch score = 2)

Effects on eye irritation: highly irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008.

Self classification:

Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is not classified for skin irritation according to the Regulation (EC) 1272/2008 (CLP) and to the Directive 67/548/EEC.

Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is classified as Eye Damage Cat. 1, H318 according to the Regulation (EC) 1272/2008 (CLP) and GHS UN, considering the persistence of eyes damages in rabbit at the end of the observation period (7 days).

Reaction product of naphthalene, propan-2-ol, sulfonated and neutralized by caustic soda is classified as STOT-SE 3, H335 according to the Regulation (EC) 1272/2008 (CLP) and GHS UN considering the irritant effects on the respiratory tract observed in the acute inhalation study in rat and the human cases reported in the manufacturing plant.