Ethyl 9,9-dioctyl-4,7,11-trioxo-3,8,10-trioxa-9-stannatetradeca-5,12-dien-14-oate

Endpoint summary

Description of key information

ACUTE ORAL TOXICITY
LD50 = 3793 mg/kg, male/female rat, OECD 401, Sarasin 1982
ACUTE DERMAL TOXICITY
LD50 = >2000 mg/kg bw, male/female rat, OECD 402, EU Method B.3, Sanders 2012

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:

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

Adequacy of study:

supporting study

Justification for type of information:

The target substance is a mono-constituent organotin substance that consists of a tin as central metal element with two octyl-ligands. The source substance Dioctyltin oxide (DOTO) (EC Number 212-791-1 and CAS 870-08-6) is also an organotin compound that has the identical structure elements as the target substance in respect of the tin-alkyl moiety.
According to WHO IPCS CIRCAD (2006) organotin compounds are characterized by a tin–carbon bond and have the general formula RxSn(L)(4−x), where R is an organic alkyl or aryl group and L is an organic (or sometimes inorganic) ligand. The organotin moiety is significant toxicologically. The anionic ligand influences physicochemical properties but generally has little or no effect on the toxicology.
Since the target substance and the source substances share the identical organotin moiety, and the organotin moiety is generally recognized as the relevant toxophore of organotins and the toxicity estimates (AE) respectively toxicity limits for organotins are expressed as tin, the overall ecotoxicity/systemic toxicity of the target can be interpolated by assessing the (eco-)toxicity of the source (WHO IPCS CIRCAD, 2006, BAUA AGS TRGS 900, 2014, Summer KH, Klein D and Greim H, 2003).
The purity of the source and target substance are expected to be similar, based on the manufacturing method. The impurity profile is not expected to have strong effects on substance properties and any impurity of (eco-)toxicological relevance of the source substances is expected to be present in the target substance. Consequently, the hazard profiles of the source substances, including those of their impurities, are intrinsically covered. Differences in impurities are not expected and thus do not have an impact on the (eco-)toxic properties.

References
BAUA (Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (Federal Institute for Occupational Safety and Health)) AGS (Ausschuss für Gefahrstoffe (Committee on Hazardous Substances)) TRGS (Technical Rules for Hazardous Substances) 900 (2014). Begründung zu n-Octylzinnverbindungen, April 2014.
Summer KH, Klein D, Griem H (2003). Ecological and toxicological aspects of mono- and disubstituted methyl-, butyl-, octyl-, and dodecyltin compounds - Update 2002. GSF National Research Center for Environment and Health, Neuherberg, for the Organotin Environmental Programme (ORTEP) Association.
World Health Organization (WHO) International Programme on Chemical Safety (IPCS) Concise International Chemical Assessment Document (CICAD) 73 Mono- and disubstituted methyltin, butyltin, and octyltin compounds (2006). Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organization, and the World Health Organization, and produced within the framework of the Inter-Organization Programme for the Sound Management of Chemicals

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

LD50

Effect level:

> 6 000 mg/kg bw

Based on:

test mat.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study pre-dates GLP inception, and was performed to a method similar to the OECD 401 guideline and to good scientific principles. The animals were only observed for 7 days prior to autopsy, but due to the high dosing, the full recovery of the animals from clinical symptoms by the 6th day and the lack of observations at autopsy, this is not thought to affect the quality of the results and conclusions. Although the reporting lacks details in some areas, it is sufficient to assess the accuracy and quality of the results and conclusions presented. The test material DOTO (di-n-octyltin oxide) is in the same category of substances as the registration substance, as such it is considered acceptable to use as additional information to address this endpoint and to provide support in the read-across approach.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(only a 7 day observation period)

GLP compliance:

no

Remarks:

study pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif.RAI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bred in the laboratory's own breeding unit
- Age at study initiation: 6 - 7 weeks old
- Weight at study initiation: 160 - 180 g
- Fasting period before study: Overnight
- Housing: Segregated into groups of 5 of the same sex, in Macralon Type 3 cages
- Diet: ad libitum (NAFAG, Gossau SG rat food)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 50 % approximate

Route of administration:

oral: unspecified

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 % suspension in the vehicle

Doses:

4640 and 6000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 6 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the study

Clinical signs:

other: 2 hours post dosing, the animals in both dosage groups exhibited sedation, dyspnoea, exophthalmus, curved position and ruffled fur. The animals were fully recovered within 5 to 6 days and autopsied on day 7.

Gross pathology:

No substance related gross organ changes were observed.

Interpretation of results:

other: Not classified according to EU criteria.

Conclusions:

Under the conditions of the test, the acute oral LD50 of the test material was found to be greater than 6000 mg/kg bw in male and female rats.

Executive summary:

The study was conducted to a guideline similar to that of the OECD 401 standardised guideline, now phased-out. The animals were dosed with the test material in polyethylene glycol at 4640 and 6000 mg/kg bw. No mortalities were observed during the test, all clinical signs observed had alleviated by day 6. Under the conditions of the test, the acute oral LD50 of the test material was found to be greater than 6000 mg/kg bw in male and female rats.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 July 1982 to 04 August 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif:RAIF(SPF), F3-crosses of RII 1/Tif x RII2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 180 - 196 g
- Housing: Groups of 5, in cages with standardised soft wood bedding
- Diet (e.g. ad libitum): Rat food, ad libitum
- Water (e.g. ad libitum): ad libitum
- Fasting period before study: Animals were fasted overnight before dosing.

ENVIRONMENTAL CONDITIONS
- Kept under conventional laboratory conditions.
- Air conditioned.
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 15 %
- Air changes (per hr): Approximately 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

Route of administration:

oral: gavage

Vehicle:

other: Distilled water containing 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight

Doses:

1000, 2500 and 5000 mg/kg

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

OBSERVATIONS
- Period: 14 days or until all symptoms have disappeared.
- Mortality: daily am and pm on working days.
- Clinical Signs: daily.
- Bodyweight: on days 1, 7, 14 and at death.
- Necropsies: spontaneously dying animals were subjected to gross necropsy as soon as possible and survivors at the termination of the study.

Statistics:

- Bodyweights: Group means and standard deviations were calculated.
- The LD50 including the 95 % confidence limit was calculated by the logit method (Berkson, 1944).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 793 mg/kg bw

Based on:

test mat.

95% CL:

2 648 - 6 646

Sex:

male

Dose descriptor:

LD50

Effect level:

3 821 mg/kg bw

Based on:

test mat.

95% CL:

2 178 - 25 811

Sex:

female

Dose descriptor:

LD50

Effect level:

3 821 mg/kg bw

Based on:

test mat.

95% CL:

2 178 - 25 811

Mortality:

4 males and 4 females died at the 5000 mg/kg dose level. All deaths occurred within 5 days post exposure. See Table 1 for details.

Clinical signs:

other: The following clinical signs were observed: sedation, dyspnoea, exophthalmus, ruffled fur and curved body position. Surviving animals recovered within 14 days. See Table 2 for details.

Gross pathology:

No treatment-related gross organ changes were observed.

Table 1 Mortality Data

Dose (mg/kg)	Totals			Time of Death
	In the Group	Deaths		Hours After Treatment				Days After Treatment
		Number	%	1	3	5	24	2	3	4	5
Males
1000	5	0
2500	5	0
5000	5	4	80						1	1	2
Females
1000	5	0
2500	5	0
5000	5	4	80				1		2	1

Table 2 Clinical Signs

Observations

Hours After Treatment

Days After Treatment

1

3

5

24

2

3

4

5

6

7

8

9

10

11

12

13

1000 mg/kg

Sedation

X

X

Dyspnoea

XX

XX

XX

XX

X

X

X

X

X

X

X

X

X

X

X

Exophthalmus

X

X

X

X

X

X

X

X

Ruffled fur

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

X

X

X

X

X

Curved body

X

X

X

X

X

X

X

X

X

X

2500 mg/kg

Sedation

X

X

X

Dyspnoea

XX

XX

XX

XX

X

X

X

X

X

X

X

X

X

X

X

Exophthalmus

X

X

X

X

X

X

X

X

X

Ruffled fur

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

X

X

X

X

X

Curved body

X

X

X

X

X

X

X

X

X

X

5000 mg/kg

Sedation

X

XX

XX

XX

XX

XX

XX

X

X

Dyspnoea

XX

XX

XX

XX

XX

XX

XX

X

X

X

X

X

X

X

X

Exophthalmus

X

X

X

X

X

X

X

Ruffled fur

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

X

Curved body

X

X

X

X

X

X

X

X

X

X

X

X

X

X

 

Table 3 Bodyweights (g)

Dose (mg/kg)	Males			Females
	Day 1	Day 7	Day 14	Day 1	Day 7	Day 14
1000	183 (4.1)	237 (6.3)	272 (6.0)	184 (3.0)	211 (7.1)	226 (12.6)
2500	185 (5.0)	199 (18.9)	246 (7.9)	188 (5.4)	196 (24.3)	222 (11.1)
5000	185 (6.5)	-	-	184 (4.1)	-	-

( ) = Standard deviation

Interpretation of results:

other: Not classified according to EU criteria.

Conclusions:

The LD50 of the test material was determined to be 3793 mg/kg in the male and female rat. The test material requires no classification in accordance with EU criteria.

Executive summary:

The acute oral toxicity of the test material was evaluated in a study conducted in accordance with the standardised guideline OECD 401.

Albino rats were administered a single oral dose of the test material by gavage at dose levels of 1000, 2500 and 5000 mg/kg bodyweight. Five animals per sex were dosed at each concentration and the animals observed for 14 days.

Four male and 4 female animals died within 5 days at the 5000 mg/kg bodyweight dose level. No further mortality was seen. Clinical signs included sedation, dyspnoea, exophthalmus, ruffled fur and exhibiting a curved body position. All survivors had recovered by the end of the observation period and no gross abnormalities were observed at necropsy.

Under the conditions of this study, the LD50 was determined to be 3793 mg/kg bodyweight and the test material requires no classification in accordance with EU criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 793 mg/kg bw

Quality of whole database:

The supporting study was performed on a read-across substance, the study was assigned a reliability score of 2 (reliable with acceptable restrictions) in accordance with the criteria for assessing data quality as outlined in Klimisch (1997). The overall quality of the dataset is considered to be high.

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:

In accordance with Column 2 (Specific rules for adaptation from Column 1), point 8.5.2 of Annex VIII, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely, taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.
Based upon the available vapour pressure of 0.13 Pa at 25 °C, exposure to the test material via inhalation is considered unlikely. Acute toxicity data has been submitted on the more appropriate routes (oral and dermal) to fulfil the data requirements for acute toxicity.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 June 2012 to 04 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

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.

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:

other: No signs of systemic toxicity were noted during the study.

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 according to 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 and the test material requires no classification in accordance with EU criteria.

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. 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.

During 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 and the test material requires no classification in accordance with EU criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The overall quality of the dataset is considered to be high.

Additional information

Acute Oral Toxicity

In the key study, the acute oral toxicity of the test material was evaluated in accordance with the standardised guideline OECD 401.

Albino rats were administered a single oral dose of the test material by gavage at dose levels of 1000, 2500 and 5000 mg/kg bodyweight. Five animals per sex were dosed at each concentration and the animals observed for 14 days.

Four male and 4 female animals died within 5 days at the 5000 mg/kg bodyweight dose level. No further mortality was seen. Clinical signs included sedation, dyspnoea, exophthalmus, ruffled fur and exhibiting a curved body position. All survivors had recovered by the end of the observation period and no gross abnormalities were observed at necropsy.

Under the conditions of this study, the LD50 was determined to be 3793 mg/kg bodyweight

Supporting information is available on the read across substance, dioctyltin (DOTO) which was used for dosing test animals, in polyethylene glycol, at 4640 and 6000 mg/kg bw. The study was conducted to a guideline similar to that of the OECD 401 standardised guideline. During the study no mortalities were observed during the test and all clinical signs observed had alleviated by day 6. Under the conditions of the test, the acute oral LD50 of the test material was found to be greater than 6000 mg/kg bw in male and female rats.

Acute Inhalation Toxicity

In accordance with Column 2 (Specific rules for adaptation from Column 1), point 8.5.2 of Annex VIII, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely, taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Based upon the available vapour pressure of 0.13 Pa at 25 °C, exposure to the test material via inhalation is considered unlikely. Acute toxicity data has been submitted on the more appropriate routes (oral and dermal) to fulfil the data requirements for acute toxicity.

Acute Dermal Toxicity

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

During 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 selection of acute toxicity – oral endpoint
The key study was conducted in compliance with agreed protocols, with no deviations from standard test guidelines and minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted to a good standard. As such the study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable as an accurate reflection of the test material.

Justification for selection of acute toxicity – inhalation endpoint
A data waiver has been submitted to address this endpoint.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available which was conducted in compliance with agreed protocols, with no deviations from standard test guidelines and minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions. As such the study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable as an accurate reflection of the test material.

Justification for classification or non-classification

The substance was demonstrated to have a high LD50 (>2000 mg/kg bw) in rats. In accordance with the Regulation (EC) No. 1272/2008 the substance does not meet the criteria for classification for acute toxicity via the oral or dermal routes.