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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Nonane-1,9-diol
EC Number:
223-517-5
EC Name:
Nonane-1,9-diol
Cas Number:
3937-56-2
Molecular formula:
C9H20O2
IUPAC Name:
nonane-1,9-diol
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%

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:
The acute median lethal oral dose to male and female rats was >2500 mg/kg bw.
Effect levelsopen allclose all
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:
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 extremities in all rats at all dose levels
- ptosis in the majority of rats dosed at 2000, 3200 and 4000 mg/kg bw and in single male and females at 5000 mg/kg bw
- prostration in many of the rats dosed at all dose levels.
Body weight:
Slightly lower bodyweight gains were recorded (refer to table below)
Gross pathology:
No treatment related effects were observed.

Any other information on results incl. tables

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

-

Applicant's summary and conclusion

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.

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