Icosyl acrylate

Endpoint summary

Description of key information

Oral

Three oral toxicity studies conducted with mixtures of long-chain acrylate esters and one study with octadecyl acrylate (C18) showed no acute toxicity after oral exposure (see table 1).

 

Table 1. Acute oral toxicity data from the source substances 

Ester	Method	Species	LD50	Reference
2-Propenoic acid, C16-18-alkyl esters [90530-21-5]	OECD TG 423	Rats	> 2000 mg/kg bw	BASF SE 2012
Octadecyl acrylate [4813-57-4]	EU B.1	Rats	> 5000 mg/kg bw	BASF SE 1985
2-Propenoic acid, C18-22-alkyl esters [85085-17-2]	OECD TG 423	Rats	> 2000 mg/kg bw	BASF SE 2012
2-Propenoic acid, C12-14-alkyl esters [84238-60-8]	OECD TG 401	Rats	> 5570 mg/kg bw	BASF AG 1964

 

The available data from the group of long-chain acrylate esters for the oral route cover all chain lengths present in the category. They are consistent and sufficient to enable an assessment for this endpoint.

 

Inhalation

The inhalation route is not of relevance due to the low vapour pressure of the substances (see chapter on Toxicokinetics).

 

Dermal

Three dermal toxicity studies conducted with mixtures of long-chain acrylate esters showed no acute toxicity after dermal application (see table 2).

 

Table 2 . Acute dermal toxicity data from the source substances 

Ester		Method	Species	LD50	Reference
2-Propenoic acid, C12-14-alkyl esters [84238-60-8]		OECD TG 402	Rat	> 5000 mg/kg bw	BASF SE 2012
2-Propenoic acid, C16-18-alkyl esters [90530-21-5]		OECD TG 402	Rat	> 5000 mg/kg bw	BASF SE 2012
2-Propenoic acid, C18-22-alkyl esters [85085-17-2]		OECD TG 402	Rat	> 5000 mg/kg bw	BASF SE 2012

 

The available data from the group of long-chain acrylate esters for the dermal route cover all chain lengths present in the category. They are consistent and sufficient to enable an assessment for this endpoint.

 

Conclusions

Acute oral toxicity studies with LD50 values above 2000 mg/kg bw and above 5000 mg/kg bw indicate a very low acute toxic potential of the long-chain alkyl acrylate esters (C12 – C22). The data on dermal toxicity of the esters in rats are indicating low dermal toxicity with LD50 values above 5000 mg/kg bw. This is in line with the low acute oral toxicity and the characteristics of skin penetration and metabolism in the skin. A skin absorption study indicates that the total amount of dodecyl methacrylate that was absorbed during the time of exposure was 0.7 % (rat epidermis) and 0.26 % (rat whole skin) over 24 hours, respectively (Jones, 2002). Hence, bearing in mind the already low acute oral toxicity, toxic effects via the dermal route are unlikely, which is confirmed by the results of the acute dermal toxicity studies with the three mixtures of long-chan alkyl acrylate esters. The inhalation route is not of relevance due to the very low vapour pressure of the substances. The studies were considered to be reliable and suitable to fulfil the REACH information requirements of Annex VII section 8.5.1 as well as Annex VIII section 8.5.2 and 8.5.3.

 

For this endpoint, the common primary metabolic pathway of the category members (i.e. common functional groups, low oral and dermal absorption and rapid metabolism by ester cleavage leading to the common metabolite AA) is considered as the most relevant aspect of the category approach. Qualitatively, this aspect can be categorised as scenario 3 “(Bio) transformation to common compound(s)”, whereas AA is the toxicologically relevant metabolite.

 

The variable part of the category approach is the length or configuration of the side chain of the parent ester and the alcohol metabolite and their impacts on physico-chemical properties and subsequent properties. Despite the variation, the available data support a lack of acute toxicity for all the category members. Overall, the read-across is applied with a high level of confidence

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2012-05-15 to 2012-06-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

(EC) No 440/2008 of 30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 423.

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay, Heidelberg

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 163 - 201 g
- Housing: Single housing, Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 10
- Photoperiod: 12 h night/12 h day

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females (1 Administration)
3 females (2 Administration)

Control animals:

no

Details on study design:

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

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed

Gross pathology:

There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period.

Under the conditions of this study the median lethal dose of Stearylacrylate, Synative MM SA, Stearyl 1618 after oral administration was found to be greater than 2000 mg/kg bw in rats.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class method, 2000 mg/kg bw of the undiluted test item were administered to two test grooups of three fasted Wistar rats by gavage.

The following test substance-related clinical observations were recorded:

2000 mg/kg:

- No mortality occured.

- No clinical signs were observed.

- The mean body weight of the surviving animals incresed within the normal range throughout the study period. Except one animal of the first test group, which showed stagnation of body weight during the second post-exposure week.

- There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period.

The acute oral LD50 was calculated to be > 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Weight at study initiation: animals of comparable weight
- Fasting period before study: no feed 16 hours before administration, water available ad libitum
- Housing: 5 animals per cage; stainless steel wire mesh cages type DK-III
- Diet: Kliba. Labordiaet, Kaiseraugst CH, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 -24 °C
- Humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: aqueous formulation corresponds to the physiological medium
- Formulation with 0.5 % aqueous carboxymethyl cellulose

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs, body weight, histopathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality

Clinical signs:

other: piloerection

Gross pathology:

No abnormalities detected.

Mortality

Animal	1 h	24 h	48 h	7 d	14 d
Male	0/5	0/5	0/5	0/5	0/5
Female	0/5	0/5	0/5	0/5	0/5

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Oct - Nov 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Remarks:

(from the competent authority) Landesamt für Umwelt, Messungen und Naturschutz Baden-Württemberg

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: Young adult animals (female approx. 9 - 10 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing
- Diet: ad libitum, VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

- Justification for choice of vehicle: Solution in olive oil Ph.Eur., good solubility in standard vehicle

DOSAGE PREPARATION: The test item preparation was produced for each application group shortly before application by stirring with a magnetic stirrer. For better handling the preparation was heated at 45 °C. The preparation was administrated hand warm

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 female animals in two test groups

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed in the first administration group during clinical examination. In the second test group only one animal showed impaired general state, dyspnoea and piloerection from hour 1 until hour 3 after administration.

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Under the conditions of this study the median lethal dose of the test item after oral administration was found to be greater than 2000 mg/kg bw in rats.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the medin lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class method, 2000 mg/kg bw of the test item (preparation in olive oil Ph. Eur.) were administered to two test groups of three fasted Wistar rats by gavage.

The following test substance-related clinical observations were recorded:

- 2000 mg/kg bw (first test group)

No mortality occured and no clinical signs were observed.

- 2000 mg/kg bw (second test group)

No mortality occured.

Impaired general state (one animal only), dyspnoea (one animal only), piloerection (one animal only).

The mean body weight increase within the normal range throughout the study period.

There were no macroscopic pathological findings at the end of the observation period.

The acute oral LD50 was therefore calculated to be > 2000 mg/kg bw.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Method: BASF-Test

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: aqueous emulsion (30%) with traganth

Doses:

0.2, 1.6, 3.2, and 6.4 mL/kg bw (corresponding to 174, 1392, 2784, and 5568 mg/kg bw)

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

The study was conducted according to an internal BASF method which in principle is comparable to the methods described in OECD Guideline 401. Several groups of 5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in aqueous emulsion with traganth.
Group-wise documentation of clinical signs was performed over the 7-day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose. The clinical signs and findings were reported in summary form. Upon completion of the study, all animals were sacrificed and submitted to gross-pathological examination.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 570 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality.

Clinical signs:

other: The animals of the highest dose group showed slight apathy and piloerection during the first 24 hours. Among the animals of the next two dose groups (2784 and 1392 mg/kg bw) slight apathy was also observed. No other clinical signs were recorded. All s

Gross pathology:

No macroscopic pathologic abnormalities were noted in the surviving animals examined at the end of the observation period.

Mortality:
----------
 Dose          No. of          Cumulative mortality after
[mg/kg bw]   animals       1 h     24 h      48 h     7 d
-----------------------------------------------------------
 5568          10         0/10     0/10      0/10     0/10
 2784          10         0/10     0/10      0/10     0/10
 1392          10         0/10     0/10      0/10     0/10
  174           10         0/10     0/10      0/10     0/10
----------------------------------------------------------- 

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study. Read across was performed with 2-Propenoic acid, C16-18-alkyl esters and Behenylacrylate. Please refer to IUCLID section 13 for read across justification.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2012-05-21 to 2012-06-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Commission Regulation (EC) No 440/2008 of 30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassy, Heidelberg

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: 243 - 249 g (male), 206 - 218 g (female)
- Housing: Single housing, Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: About 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality occurred

Clinical signs:

other: No signs of systemic toxicity were observed. The following test item-related local effects were recorded during the course of the study: - Very slight to moderate erythema (grade 1 to 3) - Very slight to slight edema (grade 1 to 2) - Incrustations

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Under the conditions of this study the median lethal dose (LD50) of Stearylacrylate, Synative MM SA, Stearyl 1618 after dermal application was found to be greater than 5000 mg/kg bw in male and female rats.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test substance after dermal application was found to be greater than 5000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10 % of the total body surface are. The animals were observed for 14 days.

No mortality occurred.

No signs of systemic toxicity were observed.

The following test item-related local effects were recorded during the course of the study:

- Very slight to moderate erythema (grade 1 to 3)

- Very slight to slight edema (grade 1 to 2)

- Incrustrations

The mean body weight of the animals increased within the normal range throughout the study period.

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 5000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Nov 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(from the competent authority) Landesamt für Umwelt, Messungen und Naturschutz Baden-Württemberg

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: young adult animals (male approx. 8 weeks, female approx. 12 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: no
- Housing: Single housing
- Diet: ad libitum, VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: 40 cm²
- % coverage: 10% of the body surface
The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
The test item preparation was produced shortly before application by stirring with a magnetic stirrer. For better handling the preparation was heated at 45°C. The preparation was administrated hand warm

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. No local effects were observed.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Under the conditions of this study the median lethal dose (LD50) of the test item after dermal application was found to be greater than 5000 mg/kg bw in male and female rats.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after dermal application was found to be greater than 5000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of the test substance (as solution in olive oil Ph. Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10 % of the total body surface area. The animals were observed for 14 days.

The following test item-related effects were recorded:

- No mortality occured

- No signs of systemic toxicity or skin effects

- The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of almost all female animals did not adequately increase during the first post-exposure week, but the females gained weight in a normal range during the second week.

- No macroscopic pahologic abnormalities

Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 5000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Oct - Nov 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Regulation (EC) No 1907/2006

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay, Labor fuer biologische Analytik GmbH

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: young adult animals (male approx. 8 weeks, female approx. 12 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight, actual weights)
- Housing: single housing
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany)
- Water: ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C
- Humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 40 cm²
- % coverage: 10% of the body surface

REMOVAL OF TEST SUBSTANCE
- Washing: yes (rinsing of the application site with warm water)
- Time after start of exposure: 24 hours after Application

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical oberservation: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. Very slight to severe erythema (grade 1 to 4). Very slight to moderate edema (grade 1 to 3). Incrustations. Severe scaling. Additionally, all local signs were noted beyond the applica

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Under the conditions of this study the median lethal dose (LD50) of Laurylacrylate 1214 after dermal application was found to be greater than 5000 mg/kg bw in male and female rats.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test substance after dermal application was found to be greater than 5000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10 % of the total body surface area. The animals were observed for 14 days.

The following test item-related effects were recorded during the course of the study:

- No mortality occured

- No signs of systemic toxicity

- Very slight to severe erythema (grade 1 to 4)

- Very slight to moderate edema (grade 1 to 3)

- Incrustrations

- Severe scaling

- Additionally, all local signs were noted beyond the application site.

- The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not adequately increase during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week...

- No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 5000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant study. Read across was performed with 2-Propenoic acid, C16-18-alkyl esters and Behenylacrylate. Please refer to IUCLID section 13 for read across justification.

Additional information

Acute oral toxicity:

In an acute oral toxicity study performed according to the standard acute method (EU B.1), 5000 mg/kg bw of the test item Octadecyl acrylate, formulated with 0.5 % aqueous carboxymethyl cellulose, were administered by gavage to a test group of 5 male and 5 female fasted Wistar rats. No mortality occurred. The acute oral LD50 was therefore calculated to be > 5000 mg/kg bw (BASF SE, 1985).

 

The mixture 2-Propenoic acid, C12-14-alkyl esters was tested according to an internal BASF method which in principle is comparable to the methods described in OECD Guideline 401. The doses were 0.2, 1.6, 3.2 and 6.4 mL/kg bw (corresponding to 174, 1392, 2784, and 5568 mg/kg bw). Several groups of 5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in aqueous emulsion with traganth. Group-wise documentation of clinical signs was performed over the 7-day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose. The clinical signs and findings were reported in summary form. Upon completion of the study, all animals were sacrificed and submitted to gross pathological examination. No mortality was revealed. The animals of the highest dose group showed slight apathy and piloerection during the first 24 hours. Among the animals of the next two dose groups (2784 and 1392 mg/kg bw) slight apathy was also observed. No other clinical signs were recorded. All symptoms disappeared within the first day of the experiment. No macroscopic pathologic abnormalities were noted in the surviving animals examined at the end of the observation period. The test substance revealed an oral LD50 > 5570 mg/kg bw (BASF SE, 1964).

 

In an acute oral toxicity study performed according to the OECD TG 423, 2000 mg/kg bw of the undiluted test item 2-Propenoic acid, C16-18-alkyl esters were administered to two test groups of three fasted female Wistar rats by gavage. The following observation period comprised 14 days. No mortality occurred and no clinical signs were observed. The mean body weight of the surviving animals increased within the normal range throughout the study period. Except one animal of the first test group, which showed stagnation of body weight during the second postexposure week. There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period. The acute oral LD50 was calculated to be > 2000 mg/kg bw (BASF SE, 2012).

 

In a further acute oral toxicity study performed according to the Acute Toxic Class method (OECD 423), 2000 mg/kg bw of the test item 2-Propenoic acid, C18-22-alkyl esters (preparation in olive oil Ph. Eur.) were administered to two test groups of three fasted female Wistar rats by gavage. The following observation period comprised 14 days. No mortality occurred in both test groups. Impaired general state, dyspnoea and piloerection were observed in one animal of the second test group only, respectively. The mean body weight increased withing the normal range throughout the study period. There were no macroscopic pathological findings at the end of the observation period. The acute oral LD50 was therefore calculated to be > 2000 mg/kg bw (BASF SE, 2012).

 

Acute inhalation studies:

The inhalation route is not of relevance due to the low vapour pressure of the substances

 

Acute dermal toxicity:

In an acute dermal toxicity study (Limit Test according to OECD 402), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of the undiluted test item 2- Propenoic acid, C12-14-alkyl esters to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10 % of the total body surface area. The animals were observed for 14 days. No mortality occurred. No signs of systemic toxicity was observed (very slight to severe erythema (grade 1 to 4), very slight to moderate edema (grade 1 to 3)). No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 5000 mg/kg bw (BASF SE, 2012).

 

In an acute dermal toxicity study (Limit Test according to OECD 402), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of the undiluted test item 2-Read Propenoic acid, C16-18-alkyl esters to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10 % of the total body surface area. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed. Very slight to moderate erythema (grade 1 to 3), very slight to slight edema (grade 1 to 2) and incrustations were recorded during the course of the study and related to the test item. The mean body weight of the animals increase within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 5000 mg/kg bw (BASF SE, 2012).

 

In another acute dermal toxicity study (Limit Test according to OECD 402), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of 2-Propenoic acid, C18-22-alkyl esters (as solution in olive oil Ph. Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10 % of the total body surface area. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity or skin effects were observed. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of almost all female animals did not adequately increase during the first post-exposure week, but the females gained weight in a normal range during the second week. No macroscopic pathologic abnormalities were observed. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 5000 mg/kg bw (BASF SE, 2012)

 

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. No mortality occured at the limit dose of 2000 mg/kg bw in oral acute toxicity studies and at the limit dose of 5000 mg/kg bw in dermal acute toxicity studies. As a result, the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No. 2017/776.