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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The data in the present report were accumulated over a period of several years.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
In general, the methods and procedures used were the same as those used in earlier work (Gaines (1960). The acute toxicity of pesticides to rats. Toxicol. Appl. Pharmacol. 2, 88-99 and
Gaines (1969). Acute toxicity of pesticides. Toxicol. Appl. Pharmacol. 14,515-534.)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Specific details on test material used for the study:
technical grade

Test animals

Species:
rat
Strain:
Sherman
Remarks:
specific-pathogen-free (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The rat colony was rederived via cesarean section and maintained under barrier conditions by the U.S. Centers for Disease Control, Atlanta, Georgia. Animals were transferred from the barrier facility at weaning and kept in conventional quarters until used.
- Age at study initiation: Adult animals were at least 90 days of age and weanlings were 4-6 weeks of age when tested.


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water and oil soluble compounds were given as solutions in water or peanut oil and poorly soluble compounds were given as suspensions in peanut oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
Adults: Whenever possible the compounds were formulated in varying concentrations and administered in volumes of 5 mL/kg bw. Dosage volumes were routinely 5-10 mL/kg for oral dosing.
Weanlings: Dosage rates up to 20 mL/kg.

Doses:
Minima of 10 animals per group and 4 dosage levels were used for each LD50 calculation.
No. of animals per sex per dose:
Minima of 10 animals per group and 4 dosage levels were used for each LD50 calculation.
Details on study design:
- Duration of observation period following administration: at least 14 days dosing or until recovered from signs of toxicity.
Statistics:
LD50 values and related parameters were calculated using a computer based implementation of Finney’s maximum likelihood probit technique (Lieberman, 1983).
A ratio of greater than 1 indicates greater toxicity to the female compared to the male or greater toxicity to the weanling compared to the adult. The LD50 ratios are considered statistically different from 1 (p < 0.05) when the 95% confidence limits of the LD50 values do not overlap.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Remarks:
adult
Effect level:
1 226 mg/kg bw
Based on:
test mat.
95% CL:
> 970 - < 1 642
Remarks on result:
other: slope: 4.2
Sex:
female
Dose descriptor:
LD50
Remarks:
adult
Effect level:
1 053 mg/kg bw
Based on:
test mat.
95% CL:
> 885 - < 1 249
Remarks on result:
other: slope: 4.6
Sex:
male
Dose descriptor:
LD50
Remarks:
weanling
Effect level:
2 232 mg/kg bw
Based on:
test mat.
95% CL:
> 1 911 - < 2 568
Remarks on result:
other: slope: 5.2
Remarks:
LD50 ratio adult/weanling: 0.55 (p<0.05)

Any other information on results incl. tables

Table 1. Acute oral toxicity of Monuron in ratsa

Common name

Ageb

 Sex

Route

LD50(mg/kg)

95% CL

(mg/kg)

Slope

LD50

(M/F)

LD50 Ratio

(A/W)

Monuron

A

M

Oral

1226

970-1642

4.2

 

 

 

A

F

Oral

1053

885-1249

4.6

1.16

 

 

W

M

Oral

2232c

1911-2568

5.2

 

0.55*

a For oral dosing, water and oil soluble compounds were given as solutions in water or peanut oil and poorly soluble compounds were given as suspensions in peanut oil.

Dosage volumes were routinely 5-10 mL/kg for oral dosing. Exceptions to the above are noted.

b A = Adult; W = Weanling.

c Dosage rates up to 20 mL/kg.

* p< 0.05.

Applicant's summary and conclusion

Conclusions:
Lowest oral LD50 in adult rats: ca. 1053 mg/kg bw.
Executive summary:

LD50 values were determined for 57 pesticides (among which Monuron) administered by the oral (or dermal) route to adult male and female Sherman rats. Monuron was also tested by the oral route in one sex of weanlings (males). Many of these and earlier LD50 tests have been done in different years and in various months of the year. Since the LD50 value is influenced by variables such as species, strain, and test method, the best estimates of relative toxicity are derived from data collected in a single species and strain under identical conditions. The values for acute toxicity reported here represent the final compilation of data for the LD50 test program whose purpose was to establish a reliable data base on the relative toxicities of pesticidal chemicals in rats, and to obtain other pertinent information including the type, onset, and duration of toxic effects following a single dose.

Except as indicated the compounds were technical grade and were dissolved or suspended in peanut oil for oral dosing (stomach tube). Water and oil soluble compounds were given as solutions in water or peanut oil and poorly soluble compounds were given as suspensions in peanut oil. Whenever possible the compounds were formulated in varying concentrations and administered in volumes of 5 mL/kg body weight for oral dosing. Because of low toxicity or poor solubility of some of the compounds, it was sometimes necessary to adjust the dose volumes as indicated. Adult animals were at least 90 days of age and weanlings were 4-6 weeks of age when tested. Minima of 10 animals per group and four dosage levels were used for each LD50 calculation. The animals were observed for at least 14 days after dosing or until recovered from signs of toxicity. LD50 values and related parameters were calculated using a computer based implementation of Finney’s maximum likelihood probit technique (Lieberman, 1983).

Consistent with previous findings (Gaines, 1960, 1969) the female rat displayed a somewhat greater susceptibility to a number of the chemicals tested. The greater drug metabolizing activity of liver microsomes in the male rat probably accounts for many of the sex-related differences in toxicity which are observed in this species. As expected, nearly all of the compounds were substantially less toxic by the dermal route than by the oral route.

For Monuron female oral LD50 was 1053 mg/kg bw with 95% confidence limits from 885-1249 mg/kg bw and male oral LD50 was 1226 mg/kg bw with 95% confidence limits from 970-1642 mg/kg bw in adult rats.

A number of other studies have demonstrated that susceptibility to the toxicity of chemicals can vary with age. We found that, of 28 chemicals for which adult/weanling oral LD50 ratios were obtained, only 14% were more toxic to the weanling while 64% were more toxic to the adult. The route of exposure may he particularly important in developing animal models of age-related toxicity.

For Monuron male oral LD50 in weanling rats was 2232 mg/kg bw with 95% confidence limits from 1911-2568 mg/kg bw. The LD50 ratio Adult/Weanling was 0.55 (p < 0.05). (Gaines and Linder, 1986).