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Description of key information

The oral LD50 determined for 6-Chloro-1-hexanol by OECD 423 method is greater than 2000 mg/kg b.w


The dermal LD50 determined for 6-Chloro-1-hexanol by OECD 402 method is greater than 2000 mg/kg b.w.

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
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
Batch# 1776194
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals were received from Charles River, Stone Ridge NY, on 10 Mar 2016. Following an acclimation period of at least five days, three male and three healthy, non-pregnant and nulliparous female Sprague
Dawley rats were assigned to treatment groups without conscious bias. The animals were born on 13 Jan 2016 and 20 Jan 2016. The pretest body weight range was
278 - 299 grams for males and 184 - 208 grams for females. The animals were identified by cage notation and indelible body marks, and housed in suspended wire
cages; five per sex per cage prior to dosing and three per sex per cage following dosing. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat
Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing. Water was available ad libitum. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a
12-hour light/dark cycle, and was kept clean and vermin free.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle to three female rats and three male rats.
Doses:
Dose level of 2000 mg/kg was administered to three female rats and three male rats.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Type and Frequency of Observations
In Vivo - Animals were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for
toxicity and pharmacological effects and twice daily for mortality. Body weights were recorded
immediately pretest, weekly, at death and at termination in the survivors.
Post Mortem – Surviving animals were humanely sacrificed using CO2 and all animals were examined for
gross pathology following study termination.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two female and three male rats survived following a single 2000 mg/kg oral dose. One female rat died on Day 1.
Clinical signs:
other: Prior to death, abnormal physical signs including dyspnea, wetness of the nose/mouth and anogenital area, ataxia, hunched posture, lethargy, flaccid muscle tone, cold to touch, and lacrimation were observed. Among the survivors, dyspnea, ataxia, flaccid m
Gross pathology:
The gross necropsy of the animal that died revealed wetness of the nose/mouth and anogenital area, red fluid in the bladder and abnormalities of the gastrointestinal tract. No observable
abnormalities were observed during the gross necropsy of the surviving animals.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The oral LD50 determined for 6-Chloro-1-hexanol by OECD 423 method is greater than 2000 mg/kg b.w.
Executive summary:

The oral LD50 determined for 6-Chloro-1-hexanol by OECD 423 method  is greater than 2000 mg/kg b.w.  

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
Experimental study conducted according to OECD guideline and under GLP condition

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:
From August 20, 2020 to Octo 06, 2020
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)
Version / remarks:
2017
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: Sponsor, 191217
- Purity, including information on contaminants, isomers, etc.: 98.50 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
The Wistar Han rat was chosen as the animal model for this study as recognized by international guidelines as a recommended test system. The test method and number of were based on the test guidelines.
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Age at study initiation: Young adult animals (approximately 11-12 weeks old)
were selected
- Weight at study initiation: 220 to 226 g.
- Housing: On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm) containing sterilized wooden fibers as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles.
-- Microbiological status when known: The feed was analyzed by the supplier for nutritional components and environmental contaminants. The feed was analyzed by the supplier for nutritional components and environmental contaminants
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 44 – 70
- Air changes (per hr): > 10
- Photoperiod (hrs dark / hrs light): 12/12


Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: an area of approximately 5x7 cm on the back of the animals
was clipped.
- % coverage: The test item was applied in an area of approximately 10% of the total body
surface, i.e. approximately 18 cm² for females.
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after application period, successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL) * purity correction factor.
- Constant volume or concentration used: yes


Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for general health/mortality and moribunditytwice daily, in the morning and at the end of the working day; Post-dose observations were performed at periodic intervals on the day of dosing (at least
three times) and once daily thereafter: Animals were weighed individually on Day 1 (pre-dose), 8 and 15.
- Necropsy of survivors performed: yes/no
- Other examinations performed: irritation. The skin reactions were assessed approximately 24, 48 and 72 hours after the removal of the dressing and test item. Adjacent areas of untreated skin ofeach animal served as controls.
Preliminary study:
A range finding study was performed in order to select the dose causing no mortality or
significant toxicity to be used in the main study. One animal was dosed at 2000 mg/kg. Based on the results of the range finding study, two animals were dosed at 2000 mg/kg.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other:
Body weight:
other body weight observations
Remarks:
The body weight gain shown by the surviving animals during the observation period was within the range expected for rats used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals

All results presented in the tables of the report are calculated using values as per the raw data rounding procedure and may not be exactly reproduced from the individual data presented.
The dermal LD50 value of the test item was ranked within the following ranges: 0-50, 50-
200, 200-1000 or 1000-2000 mg/kg b.w. or as exceeding 2000 mg/kg b.w.
The results can be evaluated according to the Globally Harmonized System of Classification
and Labelling of Chemicals (GHS) of the United Nations (including all amendments) and the
Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16
December 2008 on classification, labelling and packaging of items and mixtures (including
all amendments).

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of test item in Wistar Han rats was established to exceed 2000 mg/kg body weight.
Based on these results, the test item does not have to be classified and has no obligatory
labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
Executive summary:

TThe objective of this study was to determine the potential toxicity of 6-chlorohexan-1-ol, when given by a single dermal dose.
The study was carried out based on the guideline described in:
• OECD No. 402 (2017) "Acute Dermal Toxicity".
Initially, 6-chlorohexan-1-ol was administered to a single female Wistar Han rat by a single dermal application at 2000 mg/kg body weight for 24 hours in a range finder study. Based on the results, the main study was performed by dosing two females at 2000 mg/kg. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred.
No clinical signs were noted in the animals. Furthermore, no irritation was noted for any of
the animals at any time point. The body weight gain shown by the surviving animals during the observation period was within the range expected for rats used in this type of study.
No abnormalities were found at macroscopic post mortem examination of the animals.
The dermal LD50 value of 6-chlorohexan-1-ol in Wistar Han rats was established to exceed
2000 mg/kg body weight.
Based on these results, PU-2020-905 does not have to be classified and has no obligatory
labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
Experimental study conducted according to OECD guideline and under GLP condition

Additional information

Justification for classification or non-classification