Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed prior to the implementation of GLP and OECD Guidelines, but is in compliance with the principles described in OECD Guideline 401.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
Principles of method if other than guideline:
Study was performed before the implementation of OECD Guidelines, but followed in principle the test procedure described in OECD Guideline 401.
GLP compliance:
no
Remarks:
test predated GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Name of test material:
Methoxyacetic acid

Impurities (identity and concentrations):
appr. 0.2 % formic acid
max. 0.5 % water
max. 0.1 % formaldehyde
< 0.1 % glycolic acid
< 0.1 % oxalic acid
< 0.5 % varied ester
< 0.001 % N

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male rats: 180 - 200 g in weight.
Female rats: 160 - 170 g in weight.
Rats were fasted 15 - 20 hours prior to application.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Concentration in vehicle (%): 6.81, 10.0, 14.7, 21.5, 31.6, 46.6
Application volume per dose: 10 mL/kg
Doses:
681, 1,000, 1,470, 2,150, 3,160 or 4,640 mg/kg bw
No. of animals per sex per dose:
5 rats per sex and dose
Control animals:
no
Details on study design:
Several groups of 5 rats per sex and dose were treated by gavage with preparations of the test substance in water as vehicle. The concentrations of these preparations were usually adjusted to achieve a comparable volume of 10 mL per kg bw per animal. An observation period of 14 days was chosen.
Body weight was determined before the start of the study and 2-4, 7 and 13 days after dosing, too. Clinical signs were recorded and gross pathology was performed at the end of the observation period (day 14).
Statistics:
On the basis of the observed lethality, the LD50 value was determined.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 1 470 mg/kg bw
Remarks on result:
other: Level of significance: > 1000 mg/kg bw: 10%, < 1500 mg/kg bw: 1%
Sex:
male
Dose descriptor:
LD50
Effect level:
> 1 000 - < 1 470 mg/kg bw
Remarks on result:
other: Level of significance: 5 %
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
Mortality:
681 mg/kg bw: males: 0/5; females: 0/5
1,000 mg/kg bw: males: 0/5; females: 2/5 (within 7 days)
1,470 mg/kg bw: males: 5/5 (within 2 days); females: 5/5 (within 2 days)
2,150 mg/kg bw: males: 5/5 (within 1 day); females: 5/5 (within 1 day)
3,160 mg/kg bw: males: 5/5 (within 1 day); females: 5/5 (within 1 day)
4,640 mg/kg bw: males: 5/5 (within 1 day); females: 5/5 (within 1 day)
Clinical signs:
Dyspnoea, abnormal position, rattling, apathy, tumbling, atonia, spastic gait, tonic spasms, ruffled fur, cyanosis, dehydration, bulging eye, gummy eyes, abducted extremities, paresis, grave general condition. No clinical signs were observed in animals treated with the lowest dose (681 mg/kg bw).
Body weight:
BW development of the surviving animals was not impaired.
Gross pathology:
Animals which died during the observation period:
Heart: acute dilatation, acute congestive hyperaemia
Lung: acute swelling of moderate severity,
Stomach: extensive bloody ulceration, haemorrhagic corrosive gastritis
Gut: necrosis of the mucosa, bloody contents, severe congestion of the vessels

Animals sacrificed at the end of the observation period:
Organs without findings.
Other findings:
No data.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Methoxyacetic acid is considered to be harmful following acute oral exposure.
Executive summary:

In an acute oral toxicity study, groups of Sprague-Dawley rats (5/sex, males: 180 – 200 g, females: 160 – 170 g) were given a single oral dose of Methoxyacetic acid diluted in water at doses of 681, 1000, 1470, 2150, 3160 or 4640 mg/kg bw. Animals were then observed for 14 days. Clinical signs and dissection findings were registered.

Oral LD50 Males > 1000 < 1470 mg/kg bw

Oral LD50 Females = appr. 1000 mg/kg bw

Oral LD50 Combined > 1000 < 1470 mg/kg bw

Treatment related clinical signs were dyspnoea, abnormal position, rattling, apathy, tumbling, atonia, spastic gait, tonic spasms, ruffled fur,cyanosis, dehydration, bulging eye, gummy eyes, abducted extremities, paresis, grave general condition.

Animals that died during the observation period revealed following gross pathological changes: Heart: acute dilatation, acute congestive hyperaemia, lung: acute swelling of moderate severity, stomach: extensive bloody ulceration, haemorrhagic corrosive gastritis, Gut: necrosis of the mucosa, bloody contents, severe congestion of the vessels.

No macroscopic findings were observed in animals sacrificed at the end of the observation period.

This acute oral study is classified as acceptable. This study was performed prior to the implementation of GLP and OECD Guidelines, but is in compliance with the principles described in OECD Guideline 401.