Sulfuric acid, C16-C18 (even numbered) alkyl esters, sodium salts and C16-18 (even numbered) alcohols

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

See attached read-across justification

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other: Contact laboratory protocol

GLP compliance:

no

Specific details on test material used for the study:

OTHER SPECIFICS: Tradename Alfol 14

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2,3 kg - 2,9 kg

Type of coverage:

other: occlusive (intact and abraded)

Vehicle:

other: 1% w/w gum tragacanth

Details on dermal exposure:

TEST SITE
- Area of exposure: the dose was applied to the trunk of the animals under occlusion.
- Type of wrap if used: plastic binder

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess material was washed away and the area dried with absorbent paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): maximum dose 3-4 mL/kg
- Concentration (if solution): 50% in 1% w/w gum tragacanth


VEHICLE
- Concentration (if solution):1%

Duration of exposure:

24 h

Doses:

2000, 4000 and 8000 mg/kg

No. of animals per sex per dose:

2 (1M+1F each intact and abraded)

Control animals:

no

Details on study design:

- Time after start of exposure: 24 h
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical signs of systemic toxicity and skin reactions at application site were recorded on the day of dosing and throughout the 14 day observation period.
. Body weights were recorded prior to dosing and on observation day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: skin reactions at application site

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 8 000 mg/kg bw

Mortality:

On observation days 9 and 11.
Number of deaths at each dose: abraded 0/2, 0/2 and 2/2; intact 0/2, 0/2, 0/2.

Clinical signs:

other: At 8000 mg/kg, two surviving animals showed signs of weakness, emaciation and pallor. All returned to normal within 4 days of exposure. At 24 hours after administration all animals showed slight to moderate erythema, desquamation, wrinkling and dryness. I

Gross pathology:

Animals which succumbed showed depleted visceral fatty tissue (1 rabbit), moderate dermal irritation, and desquamation at the treatment site (2 rabbits). One animal, which was sacrificed, showed a slight accumulation of clear, viscous fluid within the peritoneal cavity and crazing over the kidney cortex. In all other animals the necropsy findings were unremarkable.

Interpretation of results:

GHS criteria not met

Conclusions:

The rabbit dermal LD50 after 24 h occlusive exposure for Alfol 14 was approximately 8000 mg/kg.
All survivors showed skin irritation at the application site throughout the observation period. Signs of intoxication included weakness, emaciation and pallor.

Executive summary:

The IUCLID dataset of 1-Tetradecanol (CAS 112-72-1, Tradename Alfol 14) in the OECD SIDS Initial Assessment Profile Long Chain Alcohols describes two Klimisch 2 studies.

The study according to contract laboratory protocol, reported by Scientific Associates Inc. (1977b) in New Zealand White rabbits is reported here.

The test material Alfol 14, diluted 50% in a 1% w/w gum tragacanth was applied to the trunk of male and female rabbits for 24 h occlusive exposure at doses of 2000, 4000 and 8000 mg/kg bw. Each dose group consisted of 4 animals: 1 male and 1 female each with intact and abraded skin.

Mortality, clinical signs of systemic toxicity and skin reactions at the application site were recorded on the day of dosing and throughout the 14 day observation period. Body weights were recorded prior to dosing and on observation day 14. All decedents and survivors were subject to gross necropsy.

Mortality was observed on observation days 9 and 11.The number of deaths at each dose were: abraded 0/2, 0/2 and 2/2; intact 0/2, 0/2, 0/2.

At 24 hours after administration all animals showed slight to moderate erythema, desquamation, wrinkling and dryness. In all surviving animals desquamation and wrinkling persisted to the end of the observation period.

At 8000 mg/kg, two surviving animals showed signs of weakness, emaciation and pallor. All returned to normal within 4 days of exposure. Body weights of surviving animals showed a slight loss in 1 animal, constant weight in 1 animal and gains within expected limits in 8 animals.

Animals which succumbed showed depleted visceral fatty tissue (1 rabbit), moderate dermal irritation, and desquamation at the treatment site (2 rabbits). One animal, which was sacrificed, showed a slight accumulation of clear, viscous fluid within the peritoneal cavity and crazing over the kidney cortex. In all other animals the necropsy findings were unremarkable.

The rabbit dermal LD50 for Alfol 14 (24 hours occluded) was approximately 8000 mg/kg bw.

(Reference: Scientific Associates, Inc. 1977b Hayes Consultancy Service Bromley, Kent).

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other: Smyth et al, 1962

GLP compliance:

no

Specific details on test material used for the study:

OTHER SPECIFICS: Test substance: tetradecanol (mixed isomers)

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 -3.5 kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: entire trunk

Duration of exposure:

Not reported

Doses:

Not reported

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

male

Dose descriptor:

LD50

Effect level:

7.13 mL/kg bw

95% CL:

4.41 - 11.52

Remarks on result:

other: Equivalent to 5847 mg/kg using the density of 0.82 g/cm3.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was 7.13 mL/kg (confidence limits 4.41-11.52 mL/kg)., equivalent to 5847 mg/kg using the density of 0.82 g/cm3. Results were not reported in detail.

Executive summary:

The IUCLID dataset of 1-Tetradecanol (CAS 112-72-1, tetradecanol (mixed isomers)) in the OECD SIDS Initial Assessment Profile Long Chain Alcohols describes two Klimisch 2 acute dermal toxicity studies.

The study according to the method of Smyth et al, 1962 , reported by Smith et al. (1969) in New Zealand White rabbits is reported here. 

Tetradecanol (mixed isomers) was applied on the entire trunk of male New Zealand White rabbits under occlusion.

The rabbit dermal LD50 for tetradecanol (mixed isomers) was 7.13 mL/kg (confidence limits 4.41-11.52 mL/kg), equivalent to 5847 mg/kg using the density of 0.82 g/cm3.

(Reference: Smyth, H.F., Carpenter, C.P., Weil, C.S., Pozzani, U.C., Striegel, J.A., and Nycum, J.S. 1969. Range-finding toxicity data: List VII. Am. Ind. Hyg. Assoc. J. 30(5):470-476).

Cross-reference 3

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other: Smyth et al, 1962

GLP compliance:

no

Specific details on test material used for the study:

OTHER SPECIFICS: Test substance: icosanol (mixed isomers)

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 -3.5 kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: entire trunk

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs

Sex:

male

Dose descriptor:

LD50

Effect level:

> 20 mL/kg bw

Remarks on result:

other: >16800 mg/kg using the density of 0.84 g/cm3.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was >20 mL/kg (>16800 mg/kg using the density of 0.84 g/cm3). Results were not reported in detail.

Executive summary:

The IUCLID dataset of 1 -Eicosanol (CAS 629 -96 -9, icosanol (mixed isomers)) in the OECD SIDS Initial Assessment Profile Long Chain Alcohols describes one Klimisch 2 study according to the method of Smyth et al., 1962 in New Zealand White rabbits. 

Undiluted icosanol (mixed isomers) was applied on the entire trunk of male rabbits under occlusion. Clinical signs were recorded during a 14 day observation period.

The rabbit dermal LD50 for icosanol (mixed isomers) was >20 mL/kg (>16800 mg/kg using the density of 0.84 g/cm3).

(Reference: Smyth, H.F., Carpenter, C.P., Weil, C.S., Pozzani, U.C.,Striegel, J.A., and Nycum, J.S. 1969. Range-finding toxicity data: List VII. Hyg. Assoc. J.30(5):470-476.)

Cross-reference 4

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

according to guideline

Guideline:

other: not specified

Principles of method if other than guideline:

10 male rabbits/group were treated with a slurry of 33% aqueous C12 ASO4 Na at 150, 300, 600, 1200 or 2000 mg/kg bw for 24 hours to both intact and abraded skin.

GLP compliance:

no

Specific details on test material used for the study:

OTHER SPECIFICS: 33 % slurry of the TS

Species:

rabbit

Sex:

male

Type of coverage:

not specified

Vehicle:

water

Details on dermal exposure:

TEST SITE
both to intact and abraded skin

Duration of exposure:

24 h

Doses:

single dosing with 150, 300, 600, 1200 or 2000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 200 mg/kg bw

Based on:

act. ingr.

Mortality:

150 mg/kg bw: 1/10
300 mg/kg bw: 2/10
600 mg/kg bw: 4/10
1200 mg/kg bw: 8/10
2000 mg/kg bw: 10/10

Clinical signs:

other: tremors, tonic-clonic convulsions, respiratory failure; terminal skin appearance: slight scaling to leathery

Gross pathology:

not further specified

Mortalities were 1/10, 2/10, 4/10, 8/10 and 10/10 animals in the 150, 300, 600, 1200 or 2000 mg/kg bw groups, respectively. Clinical signs included tremors, tonic-clonic convulsions, and respiratory failure. A decrease in body weights was seen during the 14 day post-dose observation period in animals dosed with 300 or 600 mg/kg bw. At necropsy, the treated skin area appeared leathery and showed slight scaling. The LD50 was about 200 mg/kg bw, based on active ingredient.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The LD50 was about 200 mg/kg bw, based on active ingredient.

Executive summary:

The IUCLID dataset of C12-Alkylsulfate (CAS 151-21-3) in the OECD SIDS Initial Assessment Profile on Sodium dodecyl sulfate (SDS) describes the following Klimisch 2 study.

The acute dermal toxicity of Sodium dodecyl sulfate (CAS 151-21-3) was evaluated in male rabbits. Sodium dodecyl sulfate was applied as a 33% slurry in water at doses of 150, 300, 600, 1200 or 2000 mg/kg bw both to intact and abraded skin over 24 hrs. Clinical signs and mortality and body weights were observed during 14 days. Necropsy was performed on all animals (death and surviving) and gross pathological changes were noted.

Mortality was observed in 1/10, 2/10, 4/10, 8/10 and 10/10 animals at doses of 150, 300, 600, 1200 and 2000 mg/kg bw respectively.

The observed clinical signs include: tremors, tonic-clonic convulsions, respiratory failure, decrease in body weights (300 or 600 mg/kg bw). The terminal skin appearance was slight scaling to leathery. Necropsy data were not specified.

The male dermal LD50 of Sodium dodecyl sulfate was ca. 200 mg/kg bw based on active substance.

 

Reference: Carson S & Oser BL (1964) Dermal toxicity of sodium lauryl sulfate. J Soc Cosmet Chem 15, 137 – 147.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Sulfuric acid, C16-C18 (even numbered) alkyl esters, sodium salts and C16-18 (even numbered) alcohols

EC Number:

944-399-8

Cas Number:

not yet assigned

Molecular formula:

see information in structural formula

IUPAC Name:

Sulfuric acid, C16-C18 (even numbered) alkyl esters, sodium salts and C16-18 (even numbered) alcohols

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008), based on worst case LD50 values

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

When the LD50 of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008), based on worst case LD50 values, this resulted in a dermal LD50 of 2373 mg/kg bw in rats. It can therefore be concluded that the oral LD50 of the registered substance is >2000 mg/kg bw. No classification is warranted.

Executive summary:

When the LD50 of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008), based on worst case LD50 values, this resulted in a dermal LD50 of 2373 mg/kg bw in rats. It can therefore be concluded that the oral LD50 of the registered substance is >2000 mg/kg bw. No classification is warranted.