Glycollic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

IN-LIFE DATES: From: August 13, 1998 To: September 9, 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline and GLP-compliant regulatory study. Study report revised in 2010 to re-calculate the LD50 value following re-evaluation of mortality data.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycollic acid

EC Number:

201-180-5

EC Name:

Glycollic acid

Cas Number:

79-14-1

Molecular formula:

C2H4O3

IUPAC Name:

2-hydroxyacetic acid

Details on test material:

Glycolic acid 70% solution

Test animals

Species:

rat

Strain:

other: Crl:CD (SD) IGS BR rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source of rats was Charles River Laboratories, Raleigh, North Carolina, USA. Male rats were 57 or 58 days old in a body weight range of 239.5 – 267.0 g. Female rats were 78 or 79 days old in a body weight range of 203.8 – 242.9 g prior to fasting overnight from day -1 to day of dosing.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Individual doses were adjusted to take account of animal’s fasted bodyweight and the specific gravity of the test material (1.25 g/mL) to achieve the dose levels. Additionally, the doses were adjusted for purity. The rats were fasted overnight (approximately 18 hours) prior to dosing. Post exposure period was 14 days.

Doses:

1000, 2000 and 3000 mg/kg as a 70% aqueous solution
- maximum administered dose volume was 3.40 ml/kg bw

No. of animals per sex per dose:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina.
- Age at study initiation: Male rats were 57 or 58 days old and female rats were 78 or 79 days old on day of dosing.
- Weight at study initiation: Average fasting body weights were between 224 g and 234.5 g for males and between 207.1 g
and 213.5 g for females.
- Fasting period before study: Approximately 18 hours prior to dosing. Food was returned within approximately 3 hours
after dosing.
- Housing: Rats were housed singly in suspended, stainless steel, wire-mesh cages.
- Diet (e.g. ad libitum): PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: Rats were quarantined, weighed and observed for general health for 6 days.
- 10 (5 male and 5 female) per dose group
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1°C.
- Humidity (%): 50+/- 10%.
- Photoperiod (hrs dark / hrs light): Timer controlled (12-hour light/12-hour dark cycle) lighting.

Control animals:

no

Details on study design:

Daily observations (weekends and holidays excluded unless warranted by the condition of the rats) of mortality, clinical observations of toxicity or behavioural change and body weights. All rats found dead or sacrificed were necropsied.

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations for mortality, signs of illness, injury or abnormal behavior were made daily. Rats were weighed and observed for clinical signs of toxicity daily (weekends and holday excluded unless warranted by the condition of the rats).
- Necropsy of survivors performed: Yes.
- Other examinations performed: Clinical signs, body weight, mortality, gross observations
 
Statistics
Average fasting body weight, LD50 95% confidence interval, mortality ratio (deaths/exposed).

Statistics:

Method of determination of LD50 was calculated by probit analysis (Finney, D. J., Probit Analysis, 1971).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 040 mg/kg bw

95% CL:

1 443 - 2 469

Remarks on result:

other: LD50 recalculated in revised report to address death of one intermediate dose female that died following apparent dosing trauma. The LD50 was based on 100% glycolic acid dosed (adjusted for 70% purity of the test substance).

Mortality:

Mortalities at the 1000, 2000 and 3000 mg/kg dose levels were 0, 50 and 90%, respectively. Mortalities occurred up to four days after dosing. One female dosed at 2000 mg/kg bw died following apparent dosing trauma. Since the death was not directly attributable to an effect of glycolic acid this data was excluded from the calculation of the median lethal dose when the study report was revised in 2010.

Clinical signs:

other: other: Clinical signs observed included lethargy, lung noise, ocular discharge, prostrate posture, hunched posture, stained face or chin, clear oral discharge, bloating, pallor, inappetance and moribundity.

Gross pathology:

Black stomach discolouration was observed in 5 male rats at 3000 mg/kg and 1 and 4 female rats at 2000 and 3000 mg/kg, respectively. Most rats exhibiting stomach discolouration also had stomachs distended with black fluid. Brown lung discolouration, possibly due to a gavage accident, was observed in one female rat at 2000 mg/kg - the death of this rat was attributed to mal-administration rather than a result of systemic toxicity. The gross observations for the other male and female rats were non-specific and not indicative of target organ toxicity.

Other findings:

No further information.

Any other information on results incl. tables

Table               Study summary
Group	Dose level (mg/kg)	Average dose volume (mL)	Mean bodyweight (g)			% mortality
			Day 1^1	Day 7	Day 15
Male	1000	0.26	224	277.6	338.5	0
Female		0.24	208.7	240.3	258.2	0
Male	2000	0.53	234.5	239.7	321.8	40
Female		0.47	207.1	224.6^2	262^2	80
Male	3000	0.78	229.8	na	na	100
Female		0.72	213.5	243.9^2	271.1^2	80
LD50value	2040 mg/kg bw
^1= fasted body weight na – not applicable, all rats dead ^2= single surviving female

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Fasted male and female rats were dosed at 1000, 2000 and 3000 mg/kg by oral gavage administration of the test material, glycolic acid 70% solution. Clinical signs and body weights were observed over 14 days post-dose and all animals were subjected to a necropsy. Mortalities in the treatment groups were 0, 50 and 90% for the 1000, 2000 and 3000 mg/kg doses, respectively. Clinical signs observed included lethargy, lung noise, ocular discharge, prostrate posture, hunched posture, stained face or chin, clear oral discharge, bloating, pallor and moribundity. There were few signs among rats dosed at 1000 mg/kg and the primary effects at 3000 mg/kg were prostration and lethargy. The majority of decedents were found dead on day 2, with isolated deaths occurring on days 1, 3 or 4.  LD50(male and female rates combined) – 2040 mg/kg (95% confidence limits of 1443 to 2469 mg/kg).

Executive summary:

Fasted male and female rats were dosed at 1000, 2000 and 3000 mg/kg by oral gavage administration of the test material, glycolic acid 70% solution. Clinical signs and body weights were observed over 14 days post-dose and all animals were subjected to a necropsy.

Mortalities in the treatment groups were 0, 50 and 90% for the 1000, 2000 and 3000 mg/kg doses, respectively. Clinical signs observed included lethargy, lung noise, ocular discharge, prostrate posture, hunched posture, stained face or chin, clear oral discharge, bloating, pallor and moribundity. There were few signs among rats dosed at 1000 mg/kg and the primary effects at 3000 mg/kg were prostration and lethargy. The majority of decedents were found dead on day 2, with isolated deaths occurring on days 1, 3 or 4.  LD50 (male and female rates combined) – 2040 mg/kg (95% confidence limits of 1443 to 2469 mg/kg).

 

Under the conditions of this test, the oral LD50 of Glycolic Acid for male and female rats combined was 2040 mg/kg with 95% confidence limits of 1443 - 2469 mg/kg. No classification of Glycolic acid is necessary on basis of the oral acute median lethal dose in rats.