Bis[(2-ethyl-1-oxohexyl)oxy]dioctylstannane

Endpoint summary

Description of key information

Oral

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Dermal

- Read-across to structurally similar substance DOTO (Dioctyltin oxide), CAS 870-08-6

Under the conditions of the study, the acute dermal median lethal dose (LD50) of the test material in the Wistar strain of rat was determined to be greater than 2000 mg/kg bw.

- Read-across to structurally similar substance DOT bis-(ethylmaleate), CAS 68109-88-6

Under the conditions of the study, the LD50 of the test material in the Wistar strain rat was determined to be greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 October 2017 to 13 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks of age
- Weight at study initiation: 160 to 193 g
- Fasting period before study: overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Housing: animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 %
- Air changes: at least fifteen changes per hour
- Photoperiod: controlled by a time switch to give 12 hours continuous light and 12 hours darkness

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

DOSAGE PREPARATION: The formulation was warmed to 35 - 40 °C for 5 to 10 minutes to aid preparation of the solution. The test material was formulated within 2 hours of being applied to the test system.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

A single animal was treated at 300 mg/kg bw.
Five animals were treated at 2000 mg/kg bw.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

DATA EVALUATION
- Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on body weights and abnormalities noted at necropsy were also identified.
- Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Statistics:

No statistical analysis was performed in conjunction with this study.

Preliminary study:

300 MG/KG DOSE LEVEL
- Mortality: There were no deaths.
- Clinical Observations: No signs of systemic toxicity were noted during the observation period.
- Body Weight: All animals showed expected gains in body weight over the observation period.
- Necropsy: No abnormalities were noted at necropsy.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

Signs of systemic toxicity noted during the day of dosing were hunched posture and ataxia. All animals had recovered by Day 1.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Table 1: Individual Clinical Observations and Mortality Data -2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	H	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	H	H	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	H	HA	HA	HA	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	H	HA	HA	HA	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	H	HA	HA	HA	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 =  No signs of systemic toxicity

H = Hunched Posture

A = Ataxia

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis, under GLP conditions using female Wistar rats.

Following a sighting test, dosing single animals at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

During the observation period there were no deaths. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg body weight included hunched posture and ataxia. No other signs of toxicity were noted. All animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with REACH, Annex VIII, column 2 of information requirement 8.5, in addition to the oral route, for substances other than gases, the information required under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure.

Information is provided for the dermal route which is deemed to be most appropriate as inhalation of the substance is unlikely. Testing by the inhalation route is therefore omitted.

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:

13 June 2012 to 27 June 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

other: read-across target

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))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at lest 200 g (weight variation did not exceed ± 20 % of the mean weight for each sex).
- Housing: individually during 24 hour exposure period and in groups of five, by sex, for the remainder of the study in suspended solid-floor polypropylene cages.
- Diet: ad libitum
- Water: mains drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From 13 June 2012 to 27 June 2012

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: on the day before treatment the back and flanks of each animals were clipped free of hair
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material

TEST MATERIAL
- the appropriate amount of test material was moistened with arachis oil BP and applied as evenly as possible to the area of shorn skin

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed to deaths and overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and once daily thereafter. The test site was observed daily for evidence of primary irritation and scored according to Draize (1977) (see table 1 in "Any other information on material and methods incl. tables). Individual bodyweights were recorded prior to application of the test material on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

There were no signs of systemic toxicity.

Body weight:

Animals showed expected gains in bodyweight over the study period, except for one male which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

There were no signs of dermal irritation.

Table 2: Individual Bodyweights and Weekly Bodyweight Changes

Animal no. and sex	Bodyweight (g) at day			Bodyweight change (g) during week
	0	7	14	1	2
1M	309	314	328	5	14
2M	287	303	323	16	20
3M	282	305	332	23	27
4M	399	425	435	26	10
5M	367	358	380	-9	22
1F	202	204	214	2	10
2F	221	226	237	5	11
3F	217	220	232	3	12
4F	214	221	228	7	7
5F	201	202	217	1	15

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of the study, the LD50 of the test material in the Wistar strain of rat was determined to be greater than 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test material was investigated in accordance with standardised guidelines OECD 402 and EU Method B.3, under GLP conditions.

During the study, a group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Under the conditions of the study there were no deaths and no signs of systemic toxicity. Animals showed normal weight gains and there were no signs of dermal irritation. Furthermore, no abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain of rat was therefore determined to be greater than 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

Read-across to structurally similar substance dioctyltin oxide (Public name: DOTO, CAS: 870-08-6, EC: 212-791-1), see attached justification.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

13 June 2012 to 04 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

other: read-across target

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

see below

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

see below

Principles of method if other than guideline:

Due to a technical error, the day 3 clinical observations for two females were not recorded. This deviation was considered not to affect the integrity of the study.

GLP compliance:

yes (incl. QA statement)

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
- Strain: RccHan:WIST
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at least 200 g
- Housing: animals were housed individually during the 24 hour exposure period and in groups of up to 4, by sex, for the remainder of the study in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Rodent diet, ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From: 13 June 2012 To: 4 July 2012

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: on the day before treatment the back and flanks of each animal were clipped free of hair
- % coverage: approximately 10 % of the total body surface area
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material

TEST MATERIAL
- The appropriate amount of test material was moistened with arachis oil BP and applied as evenly as possible to the area of shorn skin

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females.

Control animals:

no

Details on study design:

In the absence of data suggesting the test material was toxic, one male and one female rat were initially treated with the test material at a dose level of 2000 mg/kg bodyweight. As no mortalities were noted, a further group of 4 male and 4 female animals were similarly treated at a dose level of 2000 mg/kg bodyweight to bring the total of each sex to 5.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths and overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and once daily thereafter. The test site was observed daily for evidence of primary irritation and scored according to Draize (1977). Individual bodyweights were recorded prior to application of the test material on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes. Animals were killed by cervical dislocation. All animals were subjected to gross necropsy, consisting of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

No signs of systemic toxicity were noted during the study.

Body weight:

One female showed bodyweight loss during the first week but expected gain in bodyweight during the second week and one female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. Remaining animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Signs of dermal irritation noted were very slight erythema, crust formation and desquamation. There were no signs of dermal irritation noted at the test site of one male.

Table 1: Individual Dermal Reactions

Animal no. and sex	Observation	Effects noted after initiation of exposure (days)
		1	2	3	4	5	6	7	8	9	10	11	12	13	14
1 -0 M	Erythema	1	1	1	1	1	1	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	D	D	D	Cf	Cf	Cf	Cf	D	D	0
3 -0 M	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3 -1 M	Erythema	1	0	1	1	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	D	D	0	0	0	0	0	0	0	0
3 -2 M	Erythema	1	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3 -3 M	Erythema	1	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	D	D	0	0	0	0	0	0	0	0
2 -0 F	Erythema	1	1	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
4 -0 F	Erythema	1	0	0	0	1	1	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	D	D	D	0	0	0	0	0	0	0
4 -1 F	Erythema	1	0	1	1	1	1	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	D	D	0	0	0	0	0	0	0	0
4 -2 F	Erythema	1	0	1	1	1	1	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	D	D	0	0	0	0	0	0	0	0
4 -3 F	Erythema	1	1	1	1	1	1	1	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	D	D	D	D	0	0	0	0	0	0

0 = no reactions

D = desquamation

Cf = crust formation

Table 2: Individual Bodyweights and Weekly Bodyweight Changes

Animal no. and sex	Bodyweight (g) at day			Bodyweight change (g) during week
	0	7	14	1	2
1 -0 M	350	361	376	11	15
3 -0 M	260	285	299	25	14
3 -1 M	255	276	299	21	23
3 -2 M	244	275	308	31	33
3 -3 M	234	256	289	22	33
2 -0 F	230	227	237	-3	10
4 -0 F	217	220	224	3	4
4 -1 F	200	210	218	10	8
4 -2 F	214	223	221	9	-2
4 -3 F	206	213	218	7	5

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of the study, the LD50 of the test material in the Wistar strain rat was determined to be greater than 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test material was investigated in accordance with the standardised guidelines OECD 402 and EU Method B.3, under GLP conditions.

During the study, a group of ten animals (five males and five females) was given a single 24 hour, semi-occluded dermal application of the test material to intact skin clipped free of hair at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Under the conditions of the study there were no deaths and no signs of systemic toxicity were observed. One female showed bodyweight loss during the first week but expected gain in bodyweight during the second week and one female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. Remaining animals showed expected gains in bodyweight over the study period. Signs of dermal irritation noted were very slight erythema, crust formation and desquamation. There were no signs of dermal irritation noted at the test site of one male. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was therefore determined to be greater than 2000 mg/kg bw.

Reference 4

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read-across material

Justification for type of information:

Read-across to structurally similar substance.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis, under GLP conditions using female Wistar rats. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Following a sighting test dosing single animals at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight.  Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

During the observation period there were no deaths. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg body weight included hunched posture and ataxia. No other signs of toxicity were noted. All animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Inhalation

In accordance with column 2 of section 8.5.2 of REACH, the acute toxicity by inhalation study has been omitted as scientifically unjustified on the grounds that inhalation exposure to the substance is unlikely under normal conditions of use. The acute toxicity of the substance has been determined adequately by the other routes.

Dermal

- Read-across to structurally similar substance DOTO (Dioctyltin oxide), CAS 870-08-6

The acute dermal toxicity of the test material was investigated in accordance with standardised guidelines OECD 402 and EU Method B.3, under GLP conditions.

During the study, a group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Under the conditions of the study there were no deaths and no signs of systemic toxicity. Animals showed normal weight gains and there were no signs of dermal irritation. Furthermore, no abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain of rat was therefore determined to be greater than 2000 mg/kg bw.

- Read-across to structurally similar substance DOT bis-(ethylmaleate), CAS 68109-88-6

The acute dermal toxicity of the test material was investigated in accordance with the standardised guidelines OECD 402 and EU Method B.3, under GLP conditions.

During the study, a group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application of the test material to intact skin clipped free of hair at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Under the conditions of the study there were no deaths and no signs of systemic toxicity were observed. One female showed bodyweight loss during the first week but expected gain in bodyweight during the second week and one female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. Remaining animals showed expected gains in bodyweight over the study period. Signs of dermal irritation noted were very slight erythema, crust formation and desquamation. There were no signs of dermal irritation noted at the test site of one male. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was therefore determined to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity.