Nonane-1,9-diol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Study period:

n/a

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-10-11 to 1988-11-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Chemical name: 1,9-Nonanediol
- CAS no.: 3937-56-2
- Purity: 99.9%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Weight at dosing: m: 107-154g; f: 108-137g
Source: Charles River Portage, USA
Acclimation period: 12 days
Diet: Labsure LAD 1, ad libitum. animals fasted overnight prior to dosing and ~4 h post dosing
Water: Municipal water, ad libitum
Housing: Housed 5 animals of the same sex/cage
Temperature: 22-24°C
Humidity: 56%
Air changes: 15 changes/h
Photoperiod: 12 hours light/dark

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

1% methyl cellulose

Details on oral exposure:

Refer to Details on study design

Doses:

Preliminary study: 2500 mg/kg bw (2 animals/sex)
Main study: 1260, 2000, 3200, 4000, 5000 mg/kg bw (5 animals/sex)

No. of animals per sex per dose:

Refer to Doses

Control animals:

no

Details on study design:

Animals (5/sex) were fasted overnight prior to compound administration. Animals recieved 1,9-Nonanediol as a single dose administered by oral gavage in 1% MC (dose volume 20 mL/kg bw) at 1260, 2000, 3200, 4000 or 5000 mg/kg bw. Clinical signs and body weight were monitored for 14 days following dosing. Animals were then necropsied and examined macroscopically.

Statistics:

Probit analysis

Preliminary study:

The acute median lethal oral dose to male and female rats was >2500 mg/kg bw.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 3 200 mg/kg bw

Based on:

test mat.

95% CL:

ca. 2 200 - ca. 4 800

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 3 600 mg/kg bw

Based on:

test mat.

95% CL:

ca. 2 500 - ca. 6 000

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 3 400 mg/kg bw

Based on:

test mat.

95% CL:

ca. 2 600 - ca. 4 800

Mortality:

Preliminary toxicity test:
1 male and 1 female died within 2 h of dosing

Main study:
Mortality was observed in males at 2000, 3200 and 5000 mg/kg bw and females at 3200, 4000 and 5000 mg/kg bw (refer to table below)

Clinical signs:

other: Piloerection was observed in all rats within 5 minutes of dosing. This was accompanied by: - hunched posture, abnormal gait and lethargy in the majority of rats dosed at 1260, 2000, 3200 and 4000 mg/kg bw - decreased respiration and pallor of the extremit

Gross pathology:

No treatment related effects were observed.

Table 7.2/01-1
Doses, mortality/ animals treated

Dose (mg/kg bw)	Mortality ratio males	Mortality ratio females	Mortality ratio Gender combined
Preliminary study
2500	1/2	1/2	2/4
Main study
1260	0/5	0/5	0/10
2000	4/5	0/5	5/10
3200	2/5	2/5	4/10
4000	0/5	2/4*	2/9*
5000	5/5	5/5	10/10

* single animal died due to intubation error, excluded from mortality assessment

 

Table 7.2/01-2
Main study group body weights

Parameter	Body weights (mg/kg bw)					Body weights (mg/kg bw)
	1260	2000	3200	4000	5000	1260	2000	3200	4000	5000
Day 1	118	144	142	128	116	119	124	121	124	120
Day 8	187	239	226	206	-	163	174	162	169	-
Day 15	237	299	278	261	-	187	193	183	194	-

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the rat acute oral LD50 was >2000 mg/kg bw in males and females. Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, 1,9-Nonanediol has no obligatory labelling requirement for acute oral toxicity and is unclassified

Executive summary:

In a rat acute oral toxicity study 5 male and 5 female Sprague-Dawley rats received as single oral dose (via gavage) of 1,9-Nonanediol suspended in 0.5% w/v methylcellulose at 1260, 2000, 3200, 4000 or 5200 mg/kg bw. Rats were observed for 14 days. For all rats body weights were measured and a gross necropsy was performed at the end of the observation period.

 

Treatment related clinical signs included hunched post mortem abnormal gait, ataxia and lethargy in the majority of animals dose at all levels. Group mean body weight gains were not affected. Mortality was observed in males dosed at 2000 mg/kg bw and above an in females dosed at 3200 mg/kg bw and above. No abnormalities were recorded at necropsy.

 

The EU endpoint conclusion was that the rat acute oral LD50 was >2000 mg/kg bw in males and females. Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, 1,9-Nonanediol has no obligatory labelling requirement for acute oral toxicity and is unclassified.

Materials and methods

Test guideline

Qualifier:

no guideline required

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In accordance with the ECHA Chapter R.7a guidance, a waiver is requested as 1,9 Nonanediol is neither toxic via the oral route and no evidence of systemic toxicity has been observed in either the in vivo skin irritation/corrosion test or the skin sensitisation test. Consequently the need to classify for these endpoints is not triggered. Based on these toxicological endpoints, it is scientifically rationale to submit a waiver for the acute dermal toxicity endpoint as stated in the R.7a guidance for REACh.

Executive summary:

In accordance with the ECHA Chapter R.7a guidance, a waiver is requested as 1,9 Nonanediol is neither toxic via the oral route and no evidence of systemic toxicity has been observed in either the in vivo skin irritation/corrosion test or the skin sensitisation test. Consequently the need to classify for these endpoints is not triggered. Based on these toxicological endpoints, it is scientifically rationale to submit a waiver for the acute dermal toxicity endpoint as stated in the R.7a guidance for REACh.