Aashish Pandey Presentation

Introduction to Toxicology

EV 460/660 & BI 460/660

Fall 2014

Aashish Pandey Presentation

REVIEW:Clinical toxicological investigations onacute carbofuran intoxication in dogs.

Introduction: Carbofuran (odorless, white crystalline solid) is a broad spectrum carbamate pesticide that kills insects, mites and nematodes on contact or after ingestion.

-It is used against soil and foliar pests of field, fruit, vegetable and forest crops. It is available in liquid and granular formulations.

-It is soluble in water and has a moderately lengthy soil half-life (3-60 days)

-It has a high mammalian toxicity and a low potential for bioaccumulation.

-It is highly toxic by inhalation and ingestion and moderately toxic by dermal absorption.

-Its cholinesterase- inhibiting effect is short-term and reversible.

-Accumulation of acetylcholine causes excessive neurotransmitter activity in the parasympathetic (cholinergic) nervous system and at neuromuscular (nicotinic) sites.

-Studies on dogs show that this usually results in an acute onset of clinical signs categorized into three syndromes: muscarinic (vomiting, diarrhea, salivation, lacrimation, myosis, dyspnea, and bradycardia); nicotinic (muscle tremor and twitching, paresis progressing to paralysis); and central (depression, behavioral or personality changes, hyperactivity, seizures).

-Health issues:

Toxicological effects / Status / General human health issues:
May cause testicular degeneration
May be fatal if swallowed, inhaled, or absorbed through skin
Carcinogen / No
Mutagen / No
Endocrine disrupter / Yes
Reproductive/developmental effects / Yes
Acetylcholinesterase inhibitor / Yes
Neurotoxicant / Yes
Respiratory tract irritant / No
Skin irritant / No
Eye irritant / No

Table 1: Toxicological Issues of Carbofuran

-It is highly toxic to birds and honeybees whilst having a moderate to high toxicity to most aquatic organisms. It is moderately toxic to earthworms.

The Experiment:The tested substance was the commercial preparation Carbosan 35 СТ (Agro Science – USA), containing 350 mg carbofuran (2, 3-dihydro-2, 2-dimethyl-7-benzofuranyl methyl carbamate) in 1 mL, with oral LD50 for albino rats = 10.5 mg/kg.

-The experiment was aimed at establishing the tolerance of dogs to carbofuran after acute intoxication.

-The experiments included one control and six experimental groups (total number of 42 dogs)

-The subjects were treated with increasing single doses of the preparation via an oesophageal tube. The values are shown in table 2.

-Each dose was corresponding to different LD50 oral doses for albino rats.

-The clinical status of all subjects was followed three consecutive days prior to the treatment and 1, 3, 5, 7, 24 and 48 hours after treatment/exposure.

-Rectal body temperature, heart and respiratory rates, feces and urine excretion, locomotion and perception were studied.

-Carbofuran intoxication signs in dogs were observed about 15 to 30 min after the application of the preparation and lasted 3 to 5 hours. Depending on the used dose, the most obvious clinical signs were noticed by the first hour after treatment.

-

The results:

Experimental
Group / Corresponding doses for rats mg/kg / Dose mg/kg / Clinical signs and symptoms and time of appearance
I / 1/20 LD50 / 0.525 / No signs of intoxication observed
II / 1/10 LD50 / 1.05 / About 1 hour, persisted to hour 3 and fading and disappearing to hour 5 (A)
III / 1/5 LD50 / 2.1
IV / 1/3 LD50 / 3.5 / As early as the 15th min. (A, B), severity increased with different signs and symptoms upto the 20th min. thereafter nervous signs appearing upto 45th and 60th min.(D). After treatment, symptoms continued but with decreasing intensity upto hour 5 and behavior gradually returned to normal by hour 7
V / ½ LD50 / 5.25 / As early as 5th and 7th min. similar signs and similar recovery pattern as above upto hour 5 and hour 7(A, B, C, D). However two of the treated dogs died within the first hour (E).
VI / LD50 / 10.5 / After the 5th min, signs and symptoms were of same grade, however, between 30th and 45th min., all dogs died (A, B, C, D, E).
Signs And Symptoms:
A: Polypnea, dyspnea, arrhexia, wandering gaze, restlessness, moderate, salivation, diarrhea, polydipsia, vomiting, tremor, spasms, reddened conjunctivas.
B. Depression, salivation with thick saliva discharge and miosis.
C. Staggering, wandering gaze, bruxism, vomiting, fecal and urine incontinence
D. Nervous signs such as generalized tremors, tonic-clonic spasms and convulsions; animals fell to the ground and bit the bars of the cage
E. Death

Table 2: Results of the Experiment

Questions:

1. What are the different routes of exposure to Carbofuran?
2. What are the different types of toxicological effects of Carbofuran?
3. What are the general human health issues related to Carbofuran?
4. Explain the toxicity of Carbofuran in different animals. What are the different categories of clinical signs seen in dogs?
5. How is the interspecific toxicity difference of Carbofuran shown in the experiment?