Dodecan-1-ol, ethoxylated

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

The aim of this study was to assess the toxicity potential of the given test chemical after single oral administration in rats and 14 day observation period.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dodecan-1-ol, ethoxylated

EC Number:

500-002-6

EC Name:

Dodecan-1-ol, ethoxylated

Cas Number:

9002-92-0

Molecular formula:

C58H118024

IUPAC Name:

Dodecan-1-ol, ethoxylated

Test material form:

liquid

Details on test material:

Identification: Dodecan-1-ol, ethoxylated
Appearance: Colourless clear liquid
AI Content: 99.28%
Manufactured date: December, 2012
Expiry Date: December, 2014
Storage conditions: Room temperature (20 - 30 °C)
Safety precautions: Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the Personnel.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-House Bred
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8- 10 weeks at the time of dosing. Healthy young adult animals were used for the study.
- Weight at study initiation: Minimum: 135 g Maximum: 159 g (Individual body weights were within ± 6% prior to treatment after overnight fasting)
- Fasting period before study: rat were fasted for 16 to 18 hours, prior to dosing
- Housing: The animals were housed individually in polycarbonate cages.
- Bedding:All cages were provided with corn cobs
- Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle:All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period: Animal nos. 1-3 were acclimatized for 5 days, 4-6 for 8 days and 7-9 for 12 days, prior to administration of the test item.
- Identification:The animals were marked temporarily on tail, permanently on toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number, experimental start and completion date.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.60°C; Maximum: 23.30°C
- Humidity (%): Minimum: 51.80 % ; Maximum: 64.30 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: From: April 25, 2014 To:June 26, 2014

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg and 300 mg/kg
- Amount of vehicle (if gavage): 10 ml/kg body weight

Doses:

2000 and 300 mg/kg dose level

No. of animals per sex per dose:

2000 mg/kg bw-3 female rats
300 mg/kg bw-6 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical Observation - After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Additionally, animal nos. 1-3 were observed at 6 hours post dosing. Subsequently, all surviving animals were observed once a day during the 14 day observation period.
- Mortality - All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
- Body weight - All surviving rats were weighed on days 0 (prior to dosing), 7 and 14. Animals were weighed immediately after found dead.
- Necropsy of survivors performed: yes, at the end of 14 day observation period, all surviving rats were euthanised by overdose of CO2 for external and internal observations.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

1 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, animal nos. 2 and 3 were found dead on day 1 post dosing, whereas all other animals treated with 2000 and 300 mg/kg dose level were survived througout the experimentation period.

Clinical signs:

other: At 2000mg/kg, animal no. 1 was observed with mild diarrhea at 30 minutes and 1 hour post dosing, mild lethargy at 1, 2, 3 and 4 hours, soiled anal region with feces and urine at 1, 2 and 3 hours, epistaxis at 3 hours, soiled anal region with urine at 4, 6

Gross pathology:

At 2000 mg/kg, found dead animal nos. 2 and 3 were observd with wet area around anal region during external gross pathological examination and moderate to severe red discolouration of all lobes of the lungs during internal gross pathological examination. Whereas, no external and internal gross pathological changes were seen in the other animals treated with 2000 and 300 mg/kg body weight during terminal sacrifice.

Other findings:

not specified

Any other information on results incl. tables

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

  Sex:Female

Animal No.	Group/ Dose (mg/kg)	Body Weight (gram)				Body Weight Change (%)
		Day 0	Day 7	Day 14	Found Dead	Day 0-7	Day 0-14
1	2000	136	146	175	-	7.35	28.68
2		138	-	-	129	-	-
3		135	-	-	130	-	-
4	300	143	181	190	-	26.57	32.87
5		148	176	193	-	18.92	30.41
6		145	180	200	-	24.14	37.93
7		154	186	196	-	20.78	27.27
8		159	196	206	-	23.27	29.56
9		158	185	197	-	17.09	24.68

Key:- = not applicable.             

Table 2: Summary of Animal Body Weight (g) and Body Weight Chang

Sex:Female

Group/ Dose (mg/kg)		Rats Body Weight (g)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	0-7	0-14
G1/ 2000	Mean	136.33	-	-	-	-
	SD	1.53	-	-	-	-
	n	3	-	-	-	-
G2/ 300	Mean	151.17	184.00	197.00	21.79	30.45
	SD	6.79	6.90	5.59	3.52	4.60
	n	6	6	6	6	6

Keys:- = not applicable, SD = Standard Deviation, n = Number of Animals.

Table 3: Individual Animal Clinical Signs and Symptoms

Sex:Female

Animal No.	Group/ Dose (mg/kg)	Hours (Day 0)
		1/2	1	2	3	4	6
1	G1/ 2000	49^+	49^+ 99^+ 184*	99^+ 184*	99^+ 64 184*	99^+ 184**	184**
2		1	49^+ 99^+ 184*	99^+ 184*	99^++ 21^+ 184**	99^++ 21^+ 184**	99^++ 184** 21^+
3		49^+	49+ 99^+ 184*	99^+ 184*	99^++ 21^+ 184**	99^++ 21^+ 184**	98 184**
4	G2/ 300	99^+	99^+	99^+	1	1	-
5		49^+ 99^+	49^+ 99^+	99^+	1	1	-
6		49^+ 99^+	49^+ 99^+	99^+	1	1	-
7		99^+	99^+	99^+	1	1	-
8		49^+ 99^+	49^+ 99^+	99^+	1	1	-
9		99^+	99^+	99^+	1	1	-

Keys:- = Not applicable, 1 = Normal, 21 = Ataxia, 49 = Diarrhoea, 64 = Epistaxis, 98 = Lateral recumbancy, 99 = Lethargy, 184* = Soiled anal region with feaces and urine, 184** = Soiled anal reagion with urine,⁺= mild,⁺⁺= moderate.

Table 3 (Continued): Individual Animal Clinical Signs and SymptomsSex:Female

Animal No.	Group/ Dose (mg/kg)	Days post dosing
		1	2	3	4	5	6	7	8	9	10	11	12	13	14
1	G1/ 2000	184**	1	1	1	1	1	1	1	1	1	1	1	1	1
2		155 4^+ 184** 2	-	-	-	-	-	-	-	-	-	-	-	-	-
3		98 184** 4^+ 2	-	-	-	-	-	-	-	-	-	-	-	-	-
4	G2 / 300	1	1	1	1	1	1	1	1	1	1	1	1	1	1
5		1	1	1	1	1	1	1	1	1	1	1	1	1	1
6		1	1	1	1	1	1	1	1	1	1	1	1	1	1
7		1	1	1	1	1	1	1	1	1	1	1	1	1	1
8		1	1	1	1	1	1	1	1	1	1	1	1	1	1
9		1	1	1	1	1	1	1	1	1	1	1	1	1	1

Keys:  - = Not applicable, 1 = Normal, 2 =found dead , 4 = abdominal breathing, 98 = Lateral recumbancy, 155 = Sternal recumbency, 184** = Soiled anal reagion with urine,⁺= mild.

Table 4: Individual Animal Mortality Record

 Sex:Female

Animal No.	Group/ Dose (mg/kg)	Day of Observation (Day 0 to 14)
		Morning Observations	Evening Observations
1	G1/ 2000	No mortality and morbidity	No mortality and morbidity
2		No mortality and morbidity till day 1 Found dead on day 1	No mortality and morbidity on day 0
3		No mortality and morbidity till day 1 Found dead on day 1	No mortality and morbidity on day 0
4	G1/ 300	No mortality and morbidity	No mortality and morbidity
5		No mortality and morbidity	No mortality and morbidity
6		No mortality and morbidity	No mortality and morbidity
7		No mortality and morbidity	No mortality and morbidity
8		No mortality and morbidity	No mortality and morbidity
9		No mortality and morbidity	No mortality and morbidity

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this, acute oral toxicity dose (LD50) was considered to be 1000 mg/kg body weight, when female Wistar rats were treated with the given test chemical via oral route.
CLP classification: “Category 4” LD50 > 300-2000 mg/kg body weight.

Executive summary:

Acute oral toxicity study of the given test chemical was conducted as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in female Wistar Rats. Nine female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.

Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and two animals died on day 1 post dosing, so three rats of group G2 were dosed with 300 mg/kg weight and no mortality was observed. Further, three animals of the same group G2 were dosed with 300 mg/kg weight and no mortality was observed. Hence, further dosing was stopped.

Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Animals were weighed immediately after found dead. Mean body weight of animals treated with 300 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0.

At 2000mg/kg, animal no. 1 was observed with mild diarrhoea at 30 minutes and 1 hour post dosing, mild lethargy at 1, 2, 3 and 4 hours, soiled anal region with faeces and urine at 1, 2 and 3 hours, epitasis at 3 hours, soiled anal region with urine at 4, 6 hours and on day 1, followed by normal clinical sign till day 14. Animal no. 2 was observed with normal sign at 30 minutes, mild diarrhoea at 1 hour, mild to moderate lethargy at 1, 2, 3, 4 and 6 hours, soiled anal region with faeces and urine at 1, 2 and 3 hours, mild ataxia at 3, 4 and 6 hours, soiled anal region with urine at 3, 4, 6 hours and on day 1, sternal recumbency, mild abdominal breathing and found dead on day 1. Animal no. 3 was observed with mild diarrhoea at 30 minutes and 1 hour, mild to moderate lethargy at 1, 2, 3 and 4 hours, soiled anal region with faeces and urine at 1 and 2 hours, mild ataxia at 3 and 4 hours, soiled anal region with urine at 3, 4, 6 hours and on day 1, lateral recumbency at 6 hours and on day 1, mild abdominal breathing and found dead on day 1. At 300 mg/kg, animal no. 4, 7 and 9 were observed with mild lethargy at 30 minutes, 1 and 2 hours post dosing, followed by normal clinical sign till day 14. Animal no. 5, 6 and 8 were observed with mild lethargy at 30 minutes, 1 and 2 hours, mild diarrhoea at 30 minutes and 1 hour and normal clinical sign till day 14.

At 2000 mg/kg, found dead animal nos. 2 and 3 were observed with wet area around anal region during external gross pathological examination and moderate to severe red discolouration of all lobes of the lungs during internal gross pathological examination. Whereas, no external and internal gross pathological changes were seen in the other animals treated with 2000 and 300 mg/kg body weight during terminal sacrifice.

Under the conditions of this, acute oral toxicity dose (LD50) was considered to be 1000 mg/kg body weight, when female Wistar rats were treated with the given test chemical via oral route. CLP classification: “Category 4” LD50 > 300-2000 mg/kg body weight.