Registration Dossier

Administrative data

Description of key information

Weight of Evidence approach for oral acute toxicity: OECD 401, rat: LD50 > 1232 mg/kg bw, OECD 422 study in rats: NOAEL >= 1000 mg/kg bw/day, QSAR: low acute toxicity

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
12 - 26 Aug 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Substance was tested as dissolved fraction only.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1981
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Bor: WISW (SPF TNO)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Mean weight at study initiation: 182.4 g
- Fasting period before study: animals were fasted 16 h prior to administration (over night)
- Housing: 1 - 5 animals of the same sex per cage, in stainless steel wire mesh cages
- Diet: RIO Alleindiät für Ratten (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4- 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.4639 cm³/kg
Doses:
3000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed until 6 h after dosing (clinical signs and mortality) and daily for the rest of the observation period. Body weights were recorded on Day 1, 7 and 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Based on:
test mat. (dissolved fraction)
Remarks:
50% in water
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 232 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: recalculated from 50% test material solution
Mortality:
No mortality occurred during the observation period.
Clinical signs:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No adverse effects on body weight gain could be observed.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
study cannot be used for classification
Endpoint:
acute toxicity: oral
Remarks:
: QSAR profiling of acute oral toxicity
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Justification for type of information:
1. SOFTWARE
OECD QSAR Toolbox: a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry, Burgas, Bulgaria (http://toolbox.oasis-lmc.org).

2. MODEL (incl. version number)
OECD QSAR Toolbox version 4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See description of profilers in the attached documents.

5. APPLICABILITY DOMAIN
Profilers with relevance for acute oral toxicity were selected.

6. ADEQUACY OF THE RESULT
The results may be used in a weight-of-evidence approach together with other information to reach a conclusion regarding the acute oral toxicity of the test substance.
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs
Deviations:
not applicable
Principles of method if other than guideline:
The OECD QSAR Toolbox v4.2 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry, Burgas, Bulgaria (http://toolbox.oasis-lmc.org).
GLP compliance:
no
Test type:
other: QSAR profiling
Key result
Dose descriptor:
other: Toxic hazard classification by Cramer
Remarks on result:
other: Low toxicity
Remarks:
Class I
Interpretation of results:
other: low acute oral toxicity
Conclusions:
The acute oral toxicity potential of 2-butoxyethyl sulphate was evaluated using OECD QSAR Toolbox v4.2. Profilers on toxic hazard classification by Cramer indicated low acute toxicity (Class I). Based on the QSAR profiling no acute oral toxicity is expected for 2-butoxyethyl hydrogen sulphate.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2018-02-12 to 2018-08-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
other: OECD 422
Version / remarks:
29 July 2016
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Országos Gyógyszerészeti és Élelmezés-egészégügyi Intézet
Test type:
other: short-term toxicity study
Limit test:
no
Species:
rat
Strain:
other: Han:WIST of Wistar origin
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Males: 85-90 days; Females: 85-90 days
- Weight at study initiation: Males: 315-396 g; Females: 190-230 g
- Housing: Before mating: 2 animals of the same sex/cage; Mating: 1 male and 1 female/cage; Pregnant females: individually; Males after mating: 2 animals/cage; Recovery animals: 2 or 3 animals of the same sex/cage
- Diet: ssniff® SM R/M-Z+H complete diet for rats and mice provided ad libitum
- Water: tap water provided ad libitum
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 5 mL/kg body weight
- Justification for choice of vehicle: The test item is soluble in water at the intended concentrations.
- Lot/batch no.: 1801-5512; 1801-5512; 1803-5501
Doses:
100, 300 or 1000 mg/kg bw/day
No. of animals per sex per dose:
12 animals per sex per dose
5 animals per sex for control and high dose group as recovery group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 49 days (male animals) or 50-56 days (female animals); the day of first treatment is considered as Day 0 of examination.
- Frequency of observations and weighing: General clinical observations were conducted once a day, after treatment at approximately the same time. Individual body weights were recorded on Day 0 (prior to study start) and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: yes according to OECD 422 (see details in repeated dose section)
Sex:
male/female
Dose descriptor:
other: NOAEL
Effect level:
>= 1 000 other: mg/kg bw/day
Based on:
test mat.
Mortality:
There was no mortality in the control, 100, 300 or 1000 mg/kg bw/day groups during the complete study.
Clinical signs:
Clinical signs of systemic toxicity related to the test item were not detected at any dose level at the daily or weekly detailed clinical observations or at the terminal functional observations. The behavior and physical condition of animals was not affected by the test item at any dose level (100, 300 or 1000 mg/kg bw/day) during the entire observation period.
Body weight:
The body weight development of parental animals (male and female) was not affected by the test item during the course of the pre-mating, mating, post-mating, gestation and lactation periods, as well as during the recovery period.
Gross pathology:
Macroscopic findings related to the effect of the test item were not found in male and female animals at 100, 300 or 1000 mg/kg bw/day (treatment and the recovery periods).
Other findings:
- Organ weights: There were no test item related changes in the weights (absolute and relative to body or brain weights) of brain, testes and epididymides of male animals at any dose level.
The absolute and relative weights of examined organs did not demonstrate any test item related adverse alterations in selected animals (treatment and the recovery periods).
- Histopathology: Histopathological examinations of the selected organs (ovaries, uterus, vagina, testes, epididymides, prostate and seminal vesicles with coagulating gland) did not reveal any test item related changes at 1000 mg/kg bw/day.
There were no pathologic changes in the examined organs or tissues of randomly selected male or female animals in the control or 1000 mg/kg bw/day groups (treatment and the recovery periods).
- Other observations: Hematological evaluation did not reveal adverse test item related changes in the examined parameters at 100, 300 or 1000 mg/kg bw/day (treatment and the recovery periods). There were no test item related adverse effects on the examined clinical chemistry parameters at any dose (male or female; treatment and the recovery periods).
Interpretation of results:
other: no indication of acute oral toxicity
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
13 July 2017 - 18 Oct 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February, 1987
GLP compliance:
yes (incl. certificate)
Remarks:
Országos Gyógyszerészeti és Élelmezés-egészégügyi Intézet
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Females nulliparous and non-pregnant: yes
- Age at study initiation: not reported
- Weight at study initiation: 211-238 g for males; 230-253 g for females
- Fasting period before study: not reported
- Housing: 3 animals/sex/cage during acclimatization; individually housed during study
- Diet: ssniff® SM R/M-Z+H complete diet provided ad libitum
- Water: tap water provided ad libitum
- Acclimation period: 19 days for females, 5 days for males

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of animals
- % coverage: approximately 10% area of the total body surface
- Type of wrap if used: sterile gauze pads held by with adhesive hypoallergenic plaster and wrapped with semi occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: yes; removed using appropriate vehcile
- Time after start of exposure: 24 h

TEST MATERIAL
- Concentration: 2000 mg/kg bw/day
- For solids, paste formed: no, original form
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day. Clinical observations were made at the following intervals: 1h, 5h after the treatment and once each day for 14 days thereafter. Skin reaction observations were made at 1 hour as well as 24, 48 and 72 hours after removal of the patch. The body weight was recorded on day 0 (shortly before the treatment), on day 7 and on day 15 with a precision of 1 g in main study.
- Necropsy of survivors performed: yes; after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.
Preliminary study:
No deaths were observed in the preliminary study after females were treated with 50, 200, 1000 or 2000 mg/kg bw/kg of the test item.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred after the 24-hour dermal exposure to Butylmonoglycol sulphate, Na-salt in male and female rats during the study.
Clinical signs:
No behavioral changes or signs of systemic toxicity were noted during the study. Similarly, no local symptoms (dermal irritation as erythema and edema) were observed on the treated skin of animals.
Body weight:
The mean body weight of all animals corresponded to their species and age throughout the study.
Gross pathology:
No test item related pathological changes were found during the macroscopic examination of animals.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.
Conclusions:
In summary, the acute dermal LD50 value for male and female rats was considered to be greater than 2000 mg/kg bw. Therefore, the test substance does not need to be classified for acute dermal toxicity according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute toxicity: oral

In an acute oral toxicity study (similar to OECD 401) 5 male and female rats received a 50% solution of Butylmonoglycol sulphate, Na-salt (CAS 67656 -24 -0) at 3000 mg/kg bw (Hüls AG, 1987). No mortality occurred at a dose level of 3000 mg/kg bw in neither males nor females. No clinical signs of toxicity were observed up to the end of the 14-day observation period and there were no adverse effects on body weight gain. Necropsy revealed no substance-related findings. In summary, the acute oral LD50 value for male and female rats was considered to be > 3000 mg/kg bw for the 50% solution. Recalculation to the neat test substance would result in an LD50 of > 1232 mg/kg bw. Thus, the limit dose of 2000 mg/kg bw was not reached and a final conclusion on the classification cannot be drawn.

Therefore, a weight of evidence approach with additional sub-acute test data and QSAR data is performed in order to sufficiently cover the data requirements. An OECD 422 guideline study in compliance with GLP in rats is available (Toxi-Coop, 2018). Butylmonoglycol sulphate, Na-salt was administered orally (by gavage) once daily at doses of 0 (vehicle only), 100, 300 and 1000 mg/kg body weight/day to four groups of Han:WIST of Wistar origin rats consisting of 17 animals per sex in the control and high dose and 12 animals per group in low and mid dose group. A group of vehicle (distilled water) treated animals (n = 17/sex) served as control. All animals of the parent (P) generation were dosed prior to mating (14 days) and throughout mating. In addition, males received the test item or vehicle after mating up to the day before necropsy (altogether for 49 days). Females were additionally exposed through the gestation period and up to lactation days 13-16, i.e. up to the day before necropsy (altogether for 50, 51, 52, 54, 55 or 56 days). Animals of the recovery groups were administered for 63 days. There was no mortality in control, 100, 300 or 1000 mg/kg bw/day groups during the course of study (male and female). Clinical signs of systemic toxicity related to the test item were not detected at any dose level at the daily or weekly detailed clinical observations or at the terminal functional observations. The behavior and physical condition of animals was not affected by the test item at any dose level (100, 300 or 1000 mg/kg bw/day) during the entire observation period. The body weight development of parental animals (male and female) was not affected by the test item during the course of the pre-mating, mating, post-mating, gestation and lactation periods, as well as during the recovery period. The mean daily food consumption was not affected by the test item in male or female animals at 100, 300 and 1000 mg/kg bw/day during the entire study (pre-mating, post-mating, gestation and lactation periods, as well as recovery period). Hematological evaluation did not reveal adverse test item related changes in the examined parameters at 100, 300 or 1000 mg/kg bw/day (treatment and the recovery periods). There were no test item related adverse effects on the examined clinical chemistry parameters at any dose (male or female; treatment and the recovery periods). There were no test item related changes in the serum thyroid hormone (T4 and TSH) levels at any dose (parental male and 13-day offspring). Macroscopic findings related to the effect of the test item were not found in male and female animals at 100, 300 or 1000 mg/kg bw/day (treatment and the recovery periods).

There were no test item related changes in the weights (absolute and relative to body or brain weights) of brain, testes and epididymides of male animals at any dose level.

The absolute and relative weights of examined organs did not demonstrate any test item related adverse alterations in selected animals (treatment and the recovery periods).

Histopathological examinations of the selected organs (ovaries, uterus, vagina, testes, epididymides, prostate and seminal vesicles with coagulating gland) did not reveal any test item related changes at 1000 mg/kg bw/day.

There were no pathologic changes in the examined organs or tissues of randomly selected male or female animals in the control or 1000 mg/kg bw/day groups (treatment and the recovery periods).

Based on the observations made in this toxicity study, the NOAEL is determined to be >= 1000 mg/kg bw/day.

In conclusion, an acute oral toxicity study tested up to 1232 mg butylmonoglycol sulphate, Na-salt/kg bw did not show any signs of toxicity. Furthermore, in a sub-acute toxicity study no toxicity was observed up to the highest dose tested (NOAEL >= 1000 mg/kg bw/day). Finally, the acute oral toxicity potential of 2 -butoxyethyl sulphate was evaluated using OECD QSAR Toolbox v4.2. Profilers on toxic hazard classification by Cramer indicated low acute toxicity (Class I). Based on the QSAR profiling no acute oral toxicity is expected for 2-butoxyethyl hydrogen sulphate. Taken all data together, it can be concluded that butylmonoglycol sulphate, Na-salt is not acute toxic after oral exposure.

Acute toxicity: dermal

An acute dermal toxicity study is available for the registration substance Butylmonoglycol sulphate, Na-salt (CAS 67656-24-0) which was conducted according to OECD TG 402 (Toxi-Coop, 2017). In this GLP study, a single group of male and female animals (n=5 animals/sex) exposed to the test material at a dose of 2000 mg/kg bw. No mortality occurred at a dose level of 2000 mg/kg bw in neither male nor females. No clinical signs of toxicity were recorded during the study period. No behavioral changes and no systemic toxic signs were noted during the study. The test item did not cause dermal irritation symptoms. In summary, the acute dermal LD50 value for male and female rats was considered to be > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute toxicity of butylmonoglycol sulphate, Na-salt do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.