Reaction mass of sodium hydrogen N,N-dibutyl-10-(sulphonatooxy)octadecanamidate and sodium sulphooctadecanoate

Endpoint summary

Description of key information

The oral and dermal LD50 of the test material is 4609 and 4717 mg/kg bw, respectively.

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:

1974-05-06

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)

Deviations:

yes

Remarks:

female animals only, 10 animals per group

GLP compliance:

no

Remarks:

predates GLP

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Humectol CX spezial
- Substance type: fatty acid derivative
- Physical state: liquid
- Analytical purity: no details
- Impurities (identity and concentrations): no data

Species:

rat

Strain:

Wistar

Sex:

female

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

25 % solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 %

Doses:

2500, 4000, 6300, 10000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation daily and weighing weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Statistics:

no data

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 4 609 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 808 - <= 5 578

Remarks on result:

other: Probit analysis nach Linder & Weber; Vertrauensgrenzen nach Cavalli-Sforza

Mortality:

Animals died 2 hours to 2 days after treatment
Dose Mortality
2500 0/10
4000 5/10
6300 7/10
10000 10/10

Clinical signs:

other: Animals showed piloerection, red secretion from the nose and reduced general behaviour before death. Shortly before death tonic seizures were observed.

Gross pathology:

At necropsy reddish secretion was detected in the gut of deceased animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material is not classified due to an LD 50 value of > 2000 mg/kg body weight (4609 mg/kg bw).

Executive summary:

Humectol CX special, which had the appearance of a red-brown oily liquid, was administered once as a 25 % solution in water in various doses by means of a stomach tube to female SPF Wistar rats. The test was carried out in female rats because no sex-related differences were observed in preliminary tests. For every dose, 10 rats were used. The animals’ feed was withdrawn 16 hours before application, and resumed 2 hours after application of the solution. Observation time after the application lasted 14 days. During this time, in which the animals were weighed once a week, the animals received as feed a diet of ALTROMIN 1324 from the firm of Altrogge in Lage/Lippe, Germany and mains water. Feed and water were made available at will. The animals were kept in plastic cages on wood shavings. The LD50 as determined by means of a probit analysis (method according to LINDER and WEBER) was 4609 mg test item/kg bw. The lethally poisoned animals showed bristled skin, bloody secretion from the nose and lethargic behavior. Death occurred with tetanic cramps.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 609 mg/kg bw

Quality of whole database:

2, no GLP (pre-dates GLP); female animals only; acceptable as a 28d-repeated dose study is also available

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:

2012-05-09 to 2012-06-19

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))

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:

Five male and five female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ± 20 % of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with wood flakes. The animals were housed individually during the 24 Hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The calculated volume of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10 % of the total body surface area) using a graduated syringe.

Duration of exposure:

24 hours

Doses:

Using available information on the toxicity of the test material, a single group of animals was treated as follows:
Dose Level (mg/kg/bw): 4717* (* - equivalent to 2000 mg active ingredient/kg bodyweight)
Specific Gravity: 1.031
Dose Volume (mL/kg/bw): 4.58
Number of Rats: Male (5) / Female (5)

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

no statistical analysis was performed

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 717 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95 % confidence limits not reported

Mortality:

There were no deaths

Body weight:

other body weight observations

Remarks:

Two males and two females showed bodyweight loss during the first week but expected gain in bodyweight during the second week. The remaining animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Dermal Reactions
Signs of dermal irritation noted were very slight to well defined erythema, very slight to slight oedema, blanching of the skin, light brown discolouration of the epidermis, haemorrhage of dermal capillaries, loss of skin elasticity and flexibility, crust formation, small superficial scattered scabs, hardened light brown coloured scab, scab lifting at edges to reveal dried blood, scab lifting to reveal glossy skin, scab cracking, scab undulating and glossy skin. Adverse reactions prevented accurate evaluation of oedema at the test sites of three males. Adverse reactions prevented accurate evaluation of erythema and/or oedema at the test sites of three females

Evaluation of Data

Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD₅₀) of the test item was made.

Table 1: Individual Clinical Observations and Mortality Data

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Initiation of Exposure (Hours)				Effects Noted After Initiation of Exposure (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
4717*	1 – 0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 – 1 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 – 2 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 – 3 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 – 4 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 – 0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 – 1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 – 2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 – 3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 – 4 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

*= Equivalent to 2000 mg active ingredient/kg bodyweight

0= No signs of systemic toxicity

Table 2: Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Change (g) During Week
		0	7	14	1	2
4717*	1-0 Male	264	276	304	12	28
	1-1 Male	287	299	334	12	35
	1-2 Male	258	272	297	14	25
	1-3 Male	331	330	352	-1	22
	1-4 Male	385	375	394	-10	19
	2-0 Female	216	217	227	1	10
	2-1 Female	207	202	208	-5	6
	2-2 Female	212	211	216	-1	5
	2-3 Female	200	206	211	6	5
	2-4 Female	202	204	206	2	2

*= Equivalent to 2000 mg active ingredient/kg bodyweight

Table 3: Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
4717*	1-0 Male	Killed Day 14	No abnormalities detected
	1-1 Male	Killed Day 14	No abnormalities detected
	1-2 Male	Killed Day 14	No abnormalities detected
	1-3 Male	Killed Day 14	No abnormalities detected
	1-4 Male	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected
	2-3 Female	Killed Day 14	No abnormalities detected
	2-4 Female	Killed Day 14	No abnormalities detected

*= Equivalent to 2000 mg active ingredient/kg bodyweight

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information: The acute dermal median lethal dose (LD50) of the test item was found to be greater than 4717 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight). Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 4717 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight).

Executive summary:

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted)

Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

Method: A group of ten animals (five males and five females) was given a single, 24 hour, semi‑occluded dermal application of the undiluted test item to intact skin at a dose level of 4717 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight). Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality: There were no deaths.

Clinical Observations: There were no signs of systemic toxicity.

Dermal Irritation: Signs of dermal irritation noted were very slight to well‑defined erythema, very slight to slight oedema, blanching of the skin, light brown discolouration of the epidermis, haemorrhage of dermal capillaries, loss of skin elasticity and flexibility, crust formation, scabbing, scab lifting to reveal dried blood or glossy skin, scab cracking, scab undulating and glossy skin.

Bodyweight: Two males and two females showed bodyweight loss during the first week but expected gain in bodyweight during the second week. The remaining animals showed expected gains in bodyweight over the study period.

Necropsy: No abnormalities were noted at necropsy.

Conclusion: The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 4717 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 717 mg/kg bw

Quality of whole database:

1, recent study according to current guideline under GLP

Additional information

All studies were performed with a commercial formulation containing 46.2% (w/w) of the REACH registration substance. The water content of the actual test item was 57.6% (w/w). For the substance subject to REACH registration a water content of 3.8% (w/w) was analytically determined (please refer IUCLID section 1.2).

 

 

Acute toxicity: via oral route

Humectol CX special, which had the appearance of a red-brown oily liquid, was administered once as a 25 % solution in water in various doses by means of a stomach tube to female SPF Wistar rats. The test was carried out in female rats because no sex-related differences were observed in preliminary tests. For every dose, 10 rats were used. The animals’ feed was withdrawn 16 hours before application, and resumed 2 hours after application of the solution. Observation time after the application lasted 14 days. During this time, in which the animals were weighed once a week, the animals received as feed a diet of ALTROMIN 1324 from the firm of Altrogge in Lage/Lippe, Germany and mains water. Feed and water were made available at will. The animals were kept in plastic cages on wood shavings.The LD50 as determined by means of a probit analysis (method according to LINDER and WEBER) was 4609 mg of the actual test item/kg bw, which corresponds to 2129 mg/kg bw for the REACH registration substance.The lethally poisoned animals showed bristled skin, bloody secretion from the nose and lethargic behavior. Death occurred with tetanic cramps.

 

 

Acute toxicity: via dermal route

A recent acute study with dermal expsoure of rats according to current guidelines and GLP regulations did not show any sign of systemic toxicity. Local effects were weak and transient. Signs of dermal irritation noted were very slight to well‑defined erythema, very slight to slight oedema, blanching of the skin, light brown discolouration of the epidermis, haemorrhage of dermal capillaries, loss of skin elasticity and flexibility, crust formation, scabbing, scab lifting to reveal dried blood or glossy skin, scab cracking, scab undulating and glossy skin. The acute dermal median lethal dose (LD₅₀) of the actual test item in the Wistar strain rat was found to be greater than 4717 mg/kg bodyweight, which corresponds to 2179 mg/kg bw for the REACH registration substance.

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 (EC) No.1272/2008. All studies were performed with a commercial formulation containing 46.2% (w/w) of the REACH registration substance. The water content of the actual test item was 57.6% (w/w). For the substance subject to REACH registration a water content of 3.8% (w/w) was analytically determined (please refer IUCLID section 1.2). Therefore the results for the actual test item were recalculated to obtain effect concentrations that correspond to REACH registration substance taking into account its specific water content (please see recalculated values below):

 

Acute toxicity via oral route: LD50 = 2129 mg/kg bw

Acute toxicity via dermal route: LD50 = 2179.254 mg/kg bw

 

No classification is required according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council, as amended for the eighteenth time in Regulation (EU) 2022/692) based on absence of mortality at 2000 mg active ingredient/kg bw after oral as well as dermal exposure in rats.