Reaction mass of sodium (methylbutyl and pentyl) sulfonate and sodium 1,2-bis(pentyloxycarbonyl)ethanesulphonate

Endpoint summary

Description of key information

A key oral acute toxicity study according to OECD 401 test method was performed in male rats, leading to a LD50 =4650 mg test mat./kg bw. A key dermal acute toxicity study according to OECD 402 test method was performed in male rabbits, demonstrating a LD50 > 2500 mg test mat./kg bw. Acute inhalation toxicity was waived based on exposure reasons.

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:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study non-GLP with limited data on study design, however the study was conducted to state of the art methods at that time period. The study is therefore considered adequate, reliable and relevant.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

7 days observation period

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

Not provided

Route of administration:

oral: unspecified

Vehicle:

water

Remarks:

20% aqueous solution

Doses:

10.0 g/kg, 5.0 g/kg, 2.5 g/kg, 1.25 g/kg

No. of animals per sex per dose:

5 males per dose

Control animals:

no

Details on study design:

The product (Aerosol AY) was administered to groups of young, male albino rats (5 animals per group) as an 20% aqueous solution at dosages ranging from 1.25 g/kg to 10 g/kg.

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 4 650 mg/kg bw

Based on:

act. ingr.

95% CL:

> 3 000 - < 7 250

Mortality:

Death occurred fairly promptly following lethal doses, usually within one-half to one hour.
From the number and distribution of deaths, the LD50 of the product is calculated as 4650 (3000-7250) mg/kg bw.

Clinical signs:

other: Survivors exhibited varying degrees of depression for periods up to 24 hours following the dose, but thereafter maintained a normal appearance and behavior for remainder of a 7-day observation period.

Gross pathology:

They were sacrificed at the end of this time, and gross autopsy disclosed no pathology that could be attributed to the dose.

Table 1: Aerosol AY: Single Dose to Male Albino Rats by Mouth. Product Administered as a Solution in Water, 1 mL= 0.2 g.

 

Animal Number	Body weight in Grams	Weight Change in 7 Days	Dosage in g/kg	Dose in Grams	Dose in mL of Solution	Days to Death
R 9956	93	-	10.0	0.94	4.7	<1
R 9957	107	-	10.0	1.08	5.4	<1
R 9958	111	-	10.0	1.12	5.6	<1
R 9959	110	-	10.0	1.10	5.5	<1
R 9960	102	-	10.0	1.02	5.1	<1
R 9961	110	-	5.0	0.55	2.75	<1
R 9962	106	-	5.0	0.53	2.65	<1
R 9965	105	20	5.0	0.53	2.63	S
R 9966	98	28	5.0	0.49	2.45	S
R 9967	102	34	5.0	0.51	2.55	S
R 9968	103	-	2.5	0.26	1.29	<1
R 9969	104	34	2.5	0.26	1.30	S
R 9970	106	20	2.5	0.27	1.33	S
R 9971	98	37	2.5	0.25	1.23	S
R 9972	114	49	2.5	0.29	1.43	S
R 9877	90	28	1.25	0.11	0.57	S
R 9880	92	30	1.25	0.12	0.58	S
R 9881	93	35	1.25	0.12	0.59	S
R 9884	90	26	1.25	0.11	0.57	S
R 9890	94	2	1.25	0.12	0.59	S

S= Survived

LD₅₀= 4.65 (3.00-7.25) g/kg

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of Aerosol AY dosed as a 20% aqueous solution to male albino rats is 4.65 (3.00-7.25) g/kg .

Executive summary:

The test item was administered to groups of young, male albino rats (5 animals per group) as an 20% aqueous solution at dosages ranging from 1.25 g/kg to 10 g active ingredient/kg bw. Death occurred fairly promptly following lethal doses, usually within one-half to one hour, and post-mortem examination revealed moderate to severe hemorrhage of the entire gastrointestinal tract. From the number and distribution of deaths, the LD₅₀ of the product is calculated as 4.65 (3.00-7.25) g/kg. Survivors exhibited varying degrees of depression for periods up to 24 hours following the dose, but thereafter maintained a normal appearance and behavior for remainder of a 7-day observation period. They were sacrificed at the end of this time, and gross autopsy disclosed no pathology that could be attributed to the dose.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 650 mg/kg bw

Quality of whole database:

Reliable

Acute toxicity: via inhalation route

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:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study non-GLP with limited data on study design, however the study was conducted to state of the art methods at that time period. The study is therefore considered adequate, reliable and relevant.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

Not provided

Type of coverage:

occlusive

Vehicle:

other: Aerosol AY was moistened with sufficient water to form a paste

Details on dermal exposure:

TEST SITE
- Area of exposure: closely clipped skin of the abdomen
- Type of wrap if used: a cuff of polyethylene film which encircled the trunk of the animal

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 g/kg, 5 g/kg and 10 g/kg
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): The dose was moistened with sufficient water to form a paste.

Duration of exposure:

24 hours

Doses:

dosages of 2.5g/kg, 5 g/kg and 10 g/kg ; Aerosol AY was moistened with sufficient water to form a paste.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

Two out of five rabbits died at a dosage of 10 g/kg and one out of five succumbed at 5 g/kg.

Clinical signs:

other: Moderate to severe erythema and edema were present in all cases at the end of the exposure period. The edema was greatly reduced by the second day after dosing, and has subsided almost completely by the third day. Erythema persisted to a slight degree a d

Other findings:

Moderate to severe erythema and edema were present in all cases at the end of the exposure period. The edema was greatly reduced by the second day after dosing, and has subsided almost completely by the third day. Erythema persisted to a slight degree a day or two longer.
Apart from varying degrees of depression, most animals gave no evidence of systemic toxicity on the day following that of application of the dose. On the second day, however, one animal of the 10 g/kg group exhibited extreme depression and apparent loss of control of the hind legs which were fully extended anteriorly. Altough the animal could hold his head erect, it refused or was unable to attempt movement when placed on the floor. This condition is believed to have been the result of some incidental traumatic injury rather than a consequence of the dose. The animal died on the fourth day. There was another death in the 10 g/kg group, this on the sixth day, and a death at the 5 g/kg level on the sixth day. An LD50 of the product cannot be calculated from these results, although it is certainly greater than 2.5 g/kg. Survivors were observed for a total of seven days after that of the dose, and were then sacrificed. No significant pathology was find by gross autopsy.

Table 1: Aerosol AY: Single Doses to Male Albino Rabbits by Skin Application. Product Administered as an Aqueous Paste Under Polyethylene Film for 24 Hours.

 

Animal Number	Body Weight in Grams	Weight Change in 7 Days	Dosages in g/kg	Dose in Grams	Days to Death
H 745	3075	-44	10.0	30.8	S
H 746	3250	-645	10.0	32.5	S
H 747	3312	-	10.0	33.1	6
H 748	3281	-	10.0	32.8	4
H 749	3301	-583	10.0	33.0	S
H 794	3203	-107	5.0	16.1	S
H 795	3383	-245	5.0	16.9	S
H 797	3668	-636	5.0	18.3	S
H 798	3625	-	5.0	18.1	6
H 799	3802	-390	5.0	19.0	S
H 804	3000	-532	2.5	7.5	S
H 805	3520	-331	2.5	8.8	S
H 806	3270	-257	2.5	8.2	S
H 807	3675	-199	2.5	9.2	S
H 808	3500	-386	2.5	8.8	S

S= Survived

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Application of dosages of 2.5 g/kg to 10 g/kg as an aqueous paste to the clipped skin of rabbits for 24 hours led to moderate to severe erythema and edema which persisted for three to four days. Two out of five rabbits died at a dosage of 10 g/kg and one out of five succumbed at 5 g/kg.
LD50 > 2500 mg/kg bw.

Executive summary:

Three groups of male albino rabbits, 5 animals per group, received single applications of the test item on the closely-clipped skin of the abdomen at dosages of 2.5 g/kg, 5 g/kg and 10 g active ingredient/kg bw, respectively.

The dose was moistened with sufficient water to form a paste, and retained in contact with the skin for 24 hours by means of a cuff of polyethylene film which was encircled the trunk of the animal. At the end of the period of exposure, the cuff and any excess of the dose were removed, and the skin examined for primary irritation.

Moderate to severe erythema and edema were present in all cases at the end of the exposure period. The edema was greatly reduced by the second day after dosing, and has subsided almost completely by the third day. Erythema persisted to a slight degree a day or two longer.

Apart from varying degrees of depression, most animals gave no evidence of systemic toxicity on the day following that of application of the dose. On the second day, however, one animal of the 10 g/kg group exhibited extreme depression and apparent loss of control of the hind legs which were fully extended anteriorly. Although the animal could hold his head erect, he refused or was unable to attempt movement when placed on the floor. This condition is believed to have been the result of some incidental traumatic injury rather than a consequence of the dose. The animal died on the fourth day. There was another death in the 10 g/kg group, this on the sixth day, and a death at the 5 g/kg level on the sixth day. An LD₅₀ of the product cannot be calculated from these results, although it is certainly greater than 2.5 g/kg. Survivors were observed for a total of seven days after that of the dose, and were than sacrificed. No significant pathology was find by gross autopsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

Reliable

Additional information

Acute oral toxicity

In a key acute oral toxicity study (Shaffer et al., 1957a) the test item was administered to groups of young, male albino rats (5 animals per group) as an 20% aqueous solution at dosages of 1250, 2500, 5000 and 10000 mg active ingredient/kg bw. Death occurred fairly promptly following lethal doses, usually within one-half to one hour, and post-mortem examination revealed moderate to severe hemorrhage of the entire gastrointestinal tract. From the number and distribution of deaths, the LD₅₀ is calculated as 4650 mg/kg bw. Survivors exhibited varying degrees of depression for periods up to 24 hours following the dose, but thereafter maintained a normal appearance and behavior for remainder of a 7-day observation period. Gross autopsy disclosed no pathology that could be attributed to the dose.

In conclusion, based on the registered substance, there is no acute oral toxicity hazard as LD50 is >2000 mg/kg bw (active ingredient).

Acute dermal toxicity

In a key acute dermal toxicity study (Shaffer et al., 1957a) three groups of male albino rabbits, 5 animals per group, received single applications of the test item on the closely-clipped skin of the abdomen at dosages of 2500, 5000 and 10000 mg active ingredient/kg bw, respectively. The dose was moistened with sufficient water to form a paste, and retained in contact with the skin for 24 hours by means of a cuff of polyethylene film which was encircled the trunk of the animal. Moderate to severe erythema and edema were present in all cases but edema was greatly reduced by the second day after dosing, and has subsided almost completely by the third day. Erythema persisted to a slight degree a day or two longer. Apart from varying degrees of depression, most animals gave no evidence of systemic toxicity on the day following that of application of the dose. There were two deaths in the 10000 mg/kg group, and one death at the 5000 mg/kg level. LD₅₀ was greater than 2500 mg/kg bw. Survivors’ results, were observed for a total of seven days after that of the dose, and were than sacrificed. No significant pathology was find by gross autopsy.

In conclusion, there is no acute dermal toxicity hazard as LD50 is >2000 mg/kg bw (active ingredient). Further information supporting the absence of acute toxicity potential is provided in the read across justification for the Di-ester category, showing that all substances in the group were negative for acute dermal toxicity (justification with data matrix separately attached in Section 13). 

Acute inhalation toxicity

The registered substance has a vapour pressure of 25 Pa (20°C) and is marketed only in non solid and non granular form, i.e., as liquid. Inhalation is unlikely and acute inhalation testing would not lead to better risk assessment, therefore the study was waived based on Column 2 (Paragraph 8.5.2) in REACH legislation 2006R1907 Annex VIII.

Justification for selection of acute toxicity – oral endpoint
Key studty

Justification for selection of acute toxicity – dermal endpoint
Key study

Justification for classification or non-classification

As LD50 values were above limit dose of 2000 mg/kg bw for oral and dermal application, classifiation is not warranted according to the CLP regulation (No. 1272/2008 of 16 December 2008).